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Publisher: John Wiley and Sons   (Total: 1589 journals)

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Showing 1 - 200 of 1589 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 164, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 6, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 267, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 10)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 148, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 34, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 278, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 138, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 219)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 222, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 47, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 89, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 207, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 246, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 52, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 320, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 5, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 408, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 21, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 4, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 141, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 6, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 243, SJR: 2.083, h-index: 125)

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Journal Cover Andrology
  [SJR: 0.979]   [H-I: 14]   [2 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 2047-2919 - ISSN (Online) 2047-2927
   Published by John Wiley and Sons Homepage  [1589 journals]
  • The association between varicocoeles and vascular disease: an analysis of
           U.S. claims data
    • Authors: N. N. Wang; K. Dallas, S. Li, L. Baker, M. L. Eisenberg
      Abstract: S‪tudies have suggested an association between varicocele, hypogonadism, and elevated oxidative stress markers, but no other health risks have been associated with varicoceles. ‬‬‬‬We sought to determine the association between varicocele and incident medical comorbidities. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬Using the Truven Health MarketScan® claims database from 2001 to 2009, we identified 4459 men with varicoceles, and 100,066 controls based on ICD-9 and CPT codes, with an average follow-up of 3.1 person years. Men with varicoceles were classified as symptomatic or asymptomatic based on co-existing diagnoses. Men with medical comorbidities present before or within 1 year of index diagnosis were excluded. Metabolic and cardiovascular outcome variables were identified via ICD-9 codes. A Cox regression analysis was used to assess incident risk of metabolic and cardiovascular disease amongst the different groups. Men with varicoceles had a higher incidence of heart disease compared to men who underwent infertility testing (HR 1.22, 95% CI: 1.03–1.45), and men who underwent vasectomy (HR 1.32, 95% CI 1.13–1.54). The varicoceles group also had a higher risk of diabetes (HR 1.73, 95% CI: 1.37–2.18) and hyperlipidemia (HR 1.15, 95% CI: 1.03–1.28) compared to the vasectomy group. Furthermore, men with symptomatic varicoceles (n = 3442) had a higher risk of heart disease, diabetes, and hyperlipidemia following diagnosis, while men with asymptomatic varicoceles (n = 1017) did not. Given the prevalence of varicoceles, further research is needed to understand the implications of a varicocele to a man's overall health.
      PubDate: 2017-12-01T15:00:01.927838-05:
      DOI: 10.1111/andr.12437
  • Effect of testosterone supplementation on nitroso-redox imbalance, cardiac
           metabolism markers, and S100 proteins expression in the heart of castrated
           male rats
    • Authors: N. Regouat; A. Cheboub, M. Benahmed, A. Belarbi, F. Hadj-Bekkouche
      Abstract: The aim of this study was to investigate the effects of castration and testosterone supplementation on nitroso-redox status, cardiac metabolism markers, and S100 proteins expression in the heart of male rats. 50 male Wistar rats were randomized into five groups with ten animals each: group 1: control intact (CON); group 2: sham operated (Sh-O); group 3: sesame oil-treated rats (S-oil); group 4: gonadoectomized (GDX); and group 5: gonadoectomized rats treated with testosterone (GDX-T) for 8 weeks. Our results showed myofibrillar weaving, apoptosis, inflammation, and fibrosis (as reflected by increased activity of MMP 9 and MMP 2) in the heart of gonadoectomized rats. Testosterone supplementation restored the normal structure of the heart. In addition, a state of nitroso-redox imbalance was observed in the heart of castrated rats with increased NO (425.1 ± 322.8 vs. 208 ± 67.06, p ˂ 0.05) and MDA (33.18 ± 9.45 vs. 22.04 ± 7.13, p ˂ 0.05) and decreased GSH levels (0.71 ± 0.13 vs. 1.09 ± 0.19, p = 0.001). Testosterone treatment leads to a re-establish of only NO levels (425.1 ± 322.8 vs. 210.4 ± 114.3, p > 0.05). Markers of cardiac metabolism showed an enhancement of LDH activity (12725 ± 4604 vs. 5381 ± 3122, p ˂ 0.05) in the heart of castrated rats. This was inversed by testosterone replacement (12725 ± 4604 vs. 5781 ± 5187, p ˂ 0.05). Furthermore, castration induced heart's accumulation of triglycerides (37.24 ± 6.17 vs. 27.88 ± 6.47, p ˂ 0.05) and total cholesterol (61.44 ± 3.59 vs. 54.11 ± 7.55, p ˂ 0.05), which were significantly reduced by testosterone supplementation (29.03 ± 2.47 vs. 37.24 ± 6.17, p ˂ 0.05) and (47.9 ± 4.15 vs. 61.44 ± 3.59, p ˂ 0.001). Cardiomyocytes of castrated rats showed a decreased immunoexpression of S100 proteins compared to control animals. A restoration of S100 proteins immunostaining in cardiomyocyte cytoplasm was observed after testosterone supplementation. These findings confirm the deleterious effects of testosterone deficiency on cardiac function and highlight the involvement of nitric oxide, metalloproteinases 2 and 9, and S100 proteins.
      PubDate: 2017-12-01T12:45:35.34097-05:0
      DOI: 10.1111/andr.12449
  • The dynamic metabolomic changes throughout mouse epididymal lumen fluid
           potentially contribute to sperm maturation
    • Authors: S.-G. Hu; A.-J. Liang, G.-X. Yao, X.-Q. Li, M. Zou, J.-W. Liu, Y. Sun
      Abstract: Epididymal lumen fluids are directly responsible for sperm maturation. However, very little is known about the molecular details of small molecule metabolites in the epididymal lumen fluids until now. Here we identified and compared the metabolic profiles of mouse caput and cauda epididymal lumen fluids using GC-MS technique. Among 236 metabolites identified in caput and cauda epididymis, 36 were significantly enriched in caput epididymis while 18 were significantly enriched in cauda epididymis. Pathway analysis identified ascorbate and aldarate metabolism and beta-alanine metabolism as most relevant pathways in caput and cauda epididymis, respectively. Ascorbate, dehydroascorbic acid and beta-alanine associated with these two pathways were firstly reported in mouse epididymal lumen fluids and might play important roles in sperm maturation.
      PubDate: 2017-12-01T12:41:03.69126-05:0
      DOI: 10.1111/andr.12434
  • Effects of the insulin-like growth factor system on testicular
           differentiation and function: a review of the literature
    • Authors: R. Cannarella; R. A. Condorelli, S. La Vignera, A. E. Calogero
      Abstract: We recently described the occurrence of cryptorchidism, oligoasthenoteratozoospermia, and genital abnormalities in patients with distal 15q chromosome structural abnormalities. This observation brought us to hypothesize that insulin-like growth factor (IGF) receptor (IGF1R), mapping on the 15q 26.3 chromosomal band, may be involved in testicular function. To further evaluate this topic, we reviewed in vitro and in vivo studies exploring the role of the IGF system [IGF1, IGF2, IGF1R, insulin receptor substrates (IRS)] at the testicular level both in animals and in humans. In animals, IGF1/IGF1R has been found to be involved in testicular development during embryogenesis, in Sertoli cell (SC) proliferation, and in germ cell (GS) proliferation and differentiation. Interestingly, IGF1R seems to mediate follicle-stimulating hormone (FSH) effects through the PI3K/AKT pathway. In humans, IGF1 directly increases testicular volume. The molecular pathways responsible for testicular differentiation and IGF1/IGF1R signaling are highly conserved among species; therefore, the IGF system may be involved in FSH signaling also in humans. We suggest a possible molecular pathway occurring in human SCs, which involves both IGF1 and FSH through the PI3K/AKT pathway. The acknowledgment of an IGF1 mediation of the FSH-induced effects may open new ways for a targeted therapy in idiopathic non-FSH-responder oligoasthenoteratozoospermia.
      PubDate: 2017-12-01T12:40:42.5407-05:00
      DOI: 10.1111/andr.12444
  • Is immunosuppression, induced by neonatal thymectomy, compatible with poor
           reproductive performance in adult male rats'
    • Authors: M. M. Ommati; N. Tanideh, B. Rezakhaniha, J. Wang, S. Sabouri, M. Vahedi, B. Dormanesh, O. Koohi Hosseinabadi, F. Rahmanifar, S. Moosapour, A. Akhlaghi, R. Heidari, M. J. Zamiri
      Abstract: With increasing knowledge that the immune system has a major impact on reproductive ‎health, the potential for cells arising in organs such as the thymus to alleviate oxidative stress ‎has been revealed. This study addresses the impact of neonatal thymectomy on male ‎reproductive function in pubertal and adult animals. Neonatal Sprague Dawley rats were allotted to four treatments consisting of fully thymectomized, partially thymectomized, intact, and sham-operated rats. Half of the rats in each treatment were sacrificed at 40 and the other half at 80 days of age. Testicular volume, ventral prostate and spleen weight, several sperm attributes (concentration, motility, livability, membrane integrity, sperm penetration into mucus, total antioxidant capacity, mitochondrial dehydrogenase activity), plasma superoxide dismutase, glutathione, and testosterone level as well as fertility decreased in thymectomized rats. Adrenal gland weight, sperm malondialdehyde level, indices of oxidative stress, sperm abnormality, testicular and sperm lipid peroxidation, protein carbonylation, and sperm reactive oxygen species generation increased in thymectomized rats. In thymectomized rats, the testes contained high levels of malondialdehyde but low levels of glutathione and ferric-reducing antioxidant power. Epididymal sperm reactive oxygen species, blood lipid peroxidation, and oxidative stress indices ‎‎in blood and spermatozoa were highest in fully thymectomized, intermediate ‎in partially thymectomized, and lowest in both pubertal and mature control rats. Blood levels of superoxide dismutase, lipid peroxidation indices, and ‎testosterone, and mitochondrial adenosine triphosphate and ‎dehydrogenase activities in epididymal spermatozoa were lowest in fully thymectomized, ‎intermediate in partially thymectomized, and highest in both pubertal and mature control rats.‎ The data indicated that increased oxidative stress and mitochondrial dysfunction might play a role in the mechanism of immunosuppression-induced testicular and sperm abnormalities.
      PubDate: 2017-12-01T12:40:32.662728-05:
      DOI: 10.1111/andr.12448
  • Effect of varicocelectomy and/or mast cells stabilizer on sperm DNA
           fragmentation in infertile patients with varicocele
    • Authors: A. Zaazaa; A. Adel, I. Fahmy, Y. Elkhiat, A. A. Awaad, T. Mostafa
      Abstract: This study aimed to assess the effect of varicocelectomy and/or mast cells (MCs) stabilizer on sperm DNA fragmentation in infertile men with varicocele (Vx). Overall, 120 infertile patients were randomized to three equal treatment arms; patients that underwent varicocelectomy, patients on 1 mg ketotifen twice daily for three months, and patients that underwent varicocelectomy followed with 1 mg ketotifen twice daily for three months. These patients were subjected to history taking, clinical examination, semen analysis, and estimation of sperm DNA fragmentation index (DFI). After 3 months, all investigated groups showed significant improvement regarding the mean total sperm count, sperm concentration, total sperm motility, and sperm normal forms percentage compared with the pre-treatment data. As well, the mean sperm DFI was significantly improved compared with the pre-treatment data; in men that underwent varicocelectomy (34.6% vs. 28.3%), in men on MC stabilizer only (33.4% vs. 27.8%), and in men that underwent varicocelectomy followed by MC stabilizer (34.3% vs. 25.1%). Sperm DFI improvement percentages showed the highest improvement in men that underwent varicocelectomy followed with MC stabilizer compared with the other two groups (26.8% vs. 18.2%, 16.8%). Sperm DFI improvement percentages showed significant increases in the infertile patients with Vx grade III compared to Vx grade II in all investigated groups. It is concluded that in infertile men associated with Vx and high sperm DFI, surgical repair followed with MCs stabilizer significantly improve sperm DFI compared with either surgical repair or MCs stabilizer alone.
      PubDate: 2017-12-01T12:40:26.183256-05:
      DOI: 10.1111/andr.12445
  • Does using testicular sperm retrieval rather than ejaculated spermatozoa
           improve reproductive outcomes in couples with previous ART failure and
           poor ovarian response' A case-controlled study
    • Authors: A.R. Gilman; G. Younes, S. Tannus, W.Y. Son, P. Chan, W. Buckett
      Abstract: The objective of this study was to assess whether testicular-retrieved spermatozoa improve reproductive outcomes compared to fresh ejaculate in women with poor ovarian response and a history of previous ART failure. The study was performed as a retrospective case–control study at a university-based reproductive center in Montreal, Quebec, Canada. Eighteen poor-responder patients were matched 3 : 1 with 54 controls. Poor responders were defined as those with ≤3 oocytes retrieved at oocyte pickup. Cases were identified as poor responders, and only those with previous IVF failure(s) as an indication for testicular-retrieved spermatozoa were included. Controls were age and cycle attempt number matched. All patients were included only once. From January 1, 2009 to December 31, 2015, all patients and controls underwent an IVF cycle using ICSI with either testicular spermatozoa or ejaculated spermatozoa, respectively. Outcomes included live birth rate, pregnancy rate, miscarriage rate, oocyte number, and embryo transfer (ET) day. The results showed live birth rates, pregnancy rates, and miscarriage rates were similar. There were fewer day 2 ETs (8.5% vs. 48.6%, p = 0.01) and more day 5 blastocyst transfers (25.0% vs. 5.4%, p = 0.05) in the testicular sperm retrieval group compared to controls and thus an overall suggestion of better embryo quality in the testicular sperm group. Overall, however, the use of testicular sperm retrieval appears to add little. Women with poor ovarian response typically have a poor prognosis with respect to live birth rates, and this is further supported in this study. The suggestion of better embryo quality in the testicular-retrieved sperm group would need to be further assessed in a larger multicentered study.
      PubDate: 2017-12-01T12:40:23.560273-05:
      DOI: 10.1111/andr.12447
  • Long-term penile morphometric alterations in patients treated with
           robot-assisted versus open radical prostatectomy
    • Authors: P. Capogrosso; E. Ventimiglia, W. Cazzaniga, A. Stabile, F. Pederzoli, L. Boeri, G. Gandaglia, F. Dehò, A. Briganti, F. Montorsi, A. Salonia
      Abstract: Neglected side effects after radical prostatectomy have been previously reported. In this context, the prevalence of penile morphometric alterations has never been assessed in robot-assisted radical prostatectomy series. We aimed to assess prevalence of and predictors of penile morphometric alterations (i.e. penile shortening or penile morphometric deformation) at long-term follow-up in patients submitted to either robot-assisted (robot-assisted radical prostatectomy) or open radical prostatectomy. Sexually active patients after either robot-assisted radical prostatectomy or open radical prostatectomy prospectively completed a 28-item questionnaire, with sensitive issues regarding sexual function, namely orgasmic functioning, climacturia and changes in morphometric characteristics of the penis. Only patients with a post-operative follow-up ≥ 24 months were included. Patients submitted to either adjuvant or salvage therapies or those who refused to comprehensively complete the questionnaire were excluded from the analyses. A propensity-score matching analysis was implemented to control for baseline differences between groups. Logistic regression models tested potential predictors of penile morphometric alterations at long-term post-operative follow-up. Overall, 67 (50%) and 67 (50%) patients were included after open radical prostatectomy or robot-assisted radical prostatectomy, respectively. Self-rated post-operative penile shortening and penile morphometric deformation were reported by 75 (56%) and 29 (22.8%) patients, respectively. Rates of penile shortening and penile morphometric deformation were not different after open radical prostatectomy and robot-assisted radical prostatectomy [all p > 0.5]. At univariable analysis, self-reported penile morphometric alterations (either penile shortening or penile morphometric deformation) were significantly associated with baseline international index of erectile function–erectile function scores, body mass index, post-operative erectile function recovery, year of surgery and type of surgery (all p 
      PubDate: 2017-12-01T12:40:21.317899-05:
      DOI: 10.1111/andr.12446
  • Surgical correction of Peyronie's disease via tunica albuginea plication:
           long-term follow-up
    • Authors: M. Seveso; S. Melegari, O. De Francesco, A. Macchi, J. Romero Otero, G. Taverna, G. Bozzini
      Abstract: Peyronie's disease (PD) is an acquired connective tissue disorder of the tunica albuginea with fibrosis and inflammation that lead to palpable plaques formation, penile curvature, and pain during erection. Patients report negative effects on main domains such as physical appearance and self-image, sexual function, and performance. The aim of this study was to evaluate plication of the albuginea outcomes after a long-term follow-up period. Between 1998 and 2006, a total of 204 patients with PD underwent surgical correction with albuginea plication technique. We obtained complete long-term follow-up data in 187 cases. The follow-up data included evaluation of curvature correction, penile shortening, sexual function, complications, and patient satisfaction. After a mean follow-up of 141 months, the most common postoperative complications were: loss of length (150 patients had a minimal penile shortening ≤1.5 cm, 37 patient between 1.5, and 3 cm, none>3 cm), recurrent or residual penile curvature (15 patients, without impairing sexual intercourse), erectile dysfunction (15 patients had IIEF-5 
      PubDate: 2017-12-01T12:35:35.474372-05:
      DOI: 10.1111/andr.12431
  • Emerging technologies for home-based semen analysis
    • Authors: S. Yu; M. Rubin, S. Geevarughese, J. S. Pino, H. F. Rodriguez, W. Asghar
      Abstract: With about 70 million cases of infertility worldwide, half of which are caused by male factors, sperm analysis is critical to determine male fertility potential. Conventional semen analysis methods involve complex and manual inspection with a microscope, and these methods are labor intensive and can take several days. Due to unavailability of rapid, convenient, and user-friendly semen analysis tools, many men do not seek medical evaluation, especially in resource-constrained settings. Furthermore, as conventional methods have to be conducted in the laboratories, many men are unwilling to be tested as a result of social stigma in certain regions of the world. One solution can be found in at-home sperm analysis, which allows men to test their semen without the hassle of going to and paying for a clinic. Herein, we examine current at-home sperm analysis technologies and compare them to the traditional laboratory-based methods. In addition, we discuss emerging sperm analysis approaches and describe their limitations and future directions.
      PubDate: 2017-12-01T12:35:29.011127-05:
      DOI: 10.1111/andr.12441
  • Is the FSHR 2039A>G variant associated with susceptibility to
           testicular germ cell cancer'
    • Authors: A. K. Bang; A. S. Busch, K. Almstrup, J. Gromoll, S. Kliesch, E. Rajpert-De Meyts, N. E. Skakkebæk, A. Juul, F. Tüttelmann, N. Jørgensen
      Abstract: Testicular germ cell cancer (TGCC) is derived from germ cell neoplasia in situ (GCNIS), which arises due to niche disturbances affecting the Sertoli cells. It is believed that exogenous endocrine factors have a crucial role in governing neoplastic transformation but on a strong hereditary background. Follicle‐stimulating hormone (FSH) is the major regulatory hormone of the Sertoli cells. FSH signalling‐related single‐nucleotide polymorphisms (SNPs) have previously been shown to affect FSH action in men at different levels. We aimed to investigate whether three FSH‐related SNPs (FSHR 2039A>G, FSHR ‐29G>A and FSHB ‐211G>T) are associated with development of TGCC. A total of 752 Danish and German patients with TGCC from two tertiary andrological referral centres were included. Three control groups comprising 2020 men from the general population, 679 fertile men and 417 infertile men, were also included. Chi‐squared test was performed to compare genotype‐ and allele frequencies. Kruskal–Wallis test was performed to compare age at diagnosis. Patients with TGCC had a higher frequency of the A‐allele of FSHR 2039A>G compared to the group of fertile men with an AA‐genotype frequency of 30.2% vs. 22.0%, respectively, p = 0.002. This variant is associated with higher FSH receptor activity. The distribution of the FSHR 2039A>G did not differ significantly between the patients with TGCC and the infertile or the general population. The frequency of the two other SNPs did not differ between patient with TGCC and any of the control groups. No differences were detected between genotypes and age distribution or histological subtype of the tumours. In conclusion, we observed that a genetic variant associated with FSHR activity may modulate the susceptibility to TGCC.
      PubDate: 2017-11-27T17:10:26.502899-05:
      DOI: 10.1111/andr.12440
  • Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders
    • Authors: K. Shiraishi; A. Shindo, A. Harada, H. Kurumizaka, H. Kimura, Y. Ohkawa, H. Matsuyama
      Abstract: Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood. Testicular biopsy specimens from 30 men (mean age: 35 years) with non‐obstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (OA) were included. An H3.5‐specific mouse monoclonal antibody recognizing an H3.5‐specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (PCNA) was performed on Bouin's solution‐fixed sections. Expression and localization of H3.5 were compared with patient background, germinal stage, and PCNA expression. In testes of patients with normal spermatogenesis, differentially expressed H3.5 was specifically localized in either spermatogonia or preleptotene/leptotene‐stage primary spermatocytes, especially during germinal stages VI–X. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in OA. Additionally, the number of H3.5‐positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in NOA testes (p 
      PubDate: 2017-11-27T17:06:54.581948-05:
      DOI: 10.1111/andr.12438
  • Naringenin attenuates highly active antiretroviral therapy‐induced sperm
           DNA fragmentations and testicular toxicity in Sprague‐Dawley rats
    • Authors: M. Y. Adana; E. N. Akang, A. I. Peter, A. I. Jegede, E. C. S. Naidu, C. Tiloke, A. A. Chuturgoon, O. O. Azu
      Abstract: Highly active antiretroviral therapy has evolved over the years, leading to a boost in the quality of life in people living with HIV and AIDS. However, growing evidence has shown that highly active antiretroviral therapy has deleterious effects on the testes and the overall reproductive capacity. Therefore, this study is to determine the adjuvant potential of Naringenin on highly active antiretroviral therapy‐induced perturbations in fertility of male Sprague‐Dawley rats. Thirty adult male Sprague‐Dawley rats were divided into six groups viz – Control; H: 30 mg/kg of highly active antiretroviral therapy (EFV, 600 mg + FTC, 200 mg + TDF, 300 mg); N40: Naringenin, 40 mg/kg; N80: Naringenin, 80 mg/kg; HN40: highly active antiretroviral therapy + Naringenin, 40 mg/kg; HN80: highly active antiretroviral therapy + Naringenin, 80 mg/kg. The rats were euthanized after 4 weeks. Results showed that there was a significant decrease in sperm count (p 
      PubDate: 2017-11-27T17:05:32.48352-05:0
      DOI: 10.1111/andr.12439
  • Increased risk of autoimmune disorders in infertile men: analysis of US
           claims data
    • Authors: W. D. Brubaker; S. Li, L. C. Baker, M. L. Eisenberg
      Abstract: Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Existing data suggest that female infertility is associated with autoimmune disorders; however, this has not been examined in men. As immune surveillance and hormonal factors can impact male fertility and autoimmunity, we sought to determine the association between male infertility and incident autoimmune disorders. We analyzed subjects from the Truven Health MarketScan claims database from 2001 to 2008. Infertile men were identified through diagnosis and treatment codes. We examined the most common immune disorders, which were identified by ICD9 diagnosis codes. Men diagnosed with an immune disorder at baseline or within 1 year of follow‐up were excluded. Infertile men were compared to vasectomized men (i.e., men who are likely fertile) and to age‐matched control (10 : 1) group using Cox regression analysis. A total of 33,077 infertile men (mean age of 33 years), 77,693 vasectomized men (mean age 35), and 330,770 age‐matched control men (mean age 33) were assembled with a total follow‐up of 1.49 M person‐years. Overall, immune disorders were rare in the group with the individual conditions occurring in
      PubDate: 2017-11-27T17:05:24.081346-05:
      DOI: 10.1111/andr.12436
  • Testosterone replacement in transgenic sickle cell mice controls priapic
           activity and upregulates PDE5 expression and eNOS activity in the penis
    • Authors: B. Musicki; S. Karakus, W. Akakpo, F. H. Silva, J. Liu, H. Chen, B. R. Zirkin, A. L. Burnett
      Abstract: Sickle cell disease (SCD)‐associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in SCD are not known. Given the critical role of androgens in erection physiology and NO synthase (NOS)/PDE5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)NOS activity and molecular abnormalities involving PDE5. Adult male transgenic Berkeley sickle cell (Sickle) and wild‐type (WT) mice were implanted with testosterone pellets, which release 1.2 μg testosterone/day for 21 days, or vehicle. After 21 days, animals underwent erectile function assessment followed by collection of blood for serum testosterone measurements, penes for molecular analysis, and seminal vesicles as testosterone‐responsive tissue. Serum testosterone levels were measured by radioimmunoassay; protein expressions of PDE5, α‐smooth muscle actin, eNOS and nNOS, and phosphorylation of PDE5 at Ser‐92, eNOS at Ser‐1177, neuronal (n) NOS at Ser‐1412, and Akt at Ser‐473 were measured by Western blot in penile tissue. Testosterone treatment reversed downregulated serum testosterone levels and increased (p 
      PubDate: 2017-11-16T17:58:06.370461-05:
      DOI: 10.1111/andr.12442
  • Expression of oestrogen receptors (GPER, ESR1, ESR2) in human ductuli
           efferentes and proximal epididymis
    • Authors: V. Rago; F. Romeo, F. Giordano, R. Malivindi, V. Pezzi, I. Casaburi, A. Carpino
      Abstract: Oestrogen targeting in the human genital ducts is still not well‐known. In fact, to date, the localization of oestrogen receptors, ESR1 and ESR2, is controversial and the presence of the membrane oestrogen receptor GPER (G protein‐coupled oestrogen receptor) is unexplored. This study has investigated the expression of GPER, ESR1, ESR2 in human ductuli efferentes and proximal caput epididymis by immunohistochemistry and Western blot analysis. Furthermore, the presence of PELP1 (proline–glutamic acid–leucine‐rich protein 1), a co‐regulator of the oestrogen receptors, was also evaluated. In ductuli efferentes, GPER and ESR1 were clearly localized in all epithelial cells, while ESR2 was evidenced only in ciliated cells. Conversely, the epithelial cells of proximal caput epididymis revealed moderate GPER immunoreactivity, the absence of ERS1 and the occasional presence of ESR2. Furthermore, PELP1 was observed in ciliated cells of ductuli efferentes and in principal cells of proximal caput epididymis. Therefore, this study firstly demonstrated the expression of GPER in human male genital ducts, revealing a new mediator of oestrogen action in these anatomical sites. ESR1 and ESR2 were differentially localized in the two genital tracts together with PELP1, but cell sites of ERs and their co‐regulator were not homogeneous. So, a different regional/cellular association of GPER with the classical oestrogen receptors was highlighted, suggesting that oestrogen action could be mediated by GPER, ESR1, ESR2 in ductuli efferentes, while by GPER and, occasionally by ESR2, in proximal caput epididymis. This study suggests that the specific oestrogen‐mediated functions in human genital ducts might result from the different local interactions of oestrogens with oestrogen receptors and their co‐regulators.
      PubDate: 2017-11-16T17:56:06.440523-05:
      DOI: 10.1111/andr.12443
  • Relationship between testosterone in serum, saliva and urine during
           treatment with intramuscular testosterone undecanoate in gender dysphoria
           and male hypogonadism
    • Authors: Y. Lood; E. Aardal-Eriksson, C. Webe, J. Ahlner, B. Ekman, J. Wahlberg
      Abstract: Long‐term testosterone replacement therapy is mainly monitored by trough levels of serum testosterone (S‐T), while urinary testosterone (U‐T) is used by forensic toxicology to evaluate testosterone doping. Testosterone in saliva (Sal‐T) may provide additional information and simplify the sample collection. We aimed to investigate the relationships between testosterone measured in saliva, serum and urine during standard treatment with 1,000 mg testosterone undecanoate (TU) every 12th week during 1 year. This was an observational study. Males with primary and secondary hypogonadism (HG; n = 23), subjects with gender dysphoria (GD FtM; n = 15) and a healthy control group of men (n = 32) were investigated. Sal‐T, S‐T and U‐T were measured before and after TU injections. Sal‐T was determined with Salimetrics® enzyme immunoassay, S‐T with Roche Elecsys® testosterone II assay and U‐T by gas chromatography‐mass spectrometry. Sal‐T correlated significantly with S‐T and calculated free testosterone in both controls and patients (HG men and GD FtM), while Sal‐T to U‐T showed weaker correlations. Trough values of Sal‐T after 12 months were significantly higher in the GD FtM group (0.77 ± 0.35 nmol/L) compared to HG men (0.53 ± 0.22 nmol/L) and controls (0.46 ± 0.15 nmol/L), while no differences between S‐T and U‐T trough values were found. Markedly elevated concentrations of salivary testosterone, 7–14 days after injection, were observed, especially in the GD FtM group. This study demonstrates that Sal‐T might be a useful clinical tool to monitor long‐term testosterone replacement therapy and might give additional information in forensic cases.
      PubDate: 2017-11-16T17:55:35.530979-05:
      DOI: 10.1111/andr.12435
  • Clinical and biochemical correlates of male hypogonadism in type 2
    • Authors: A. Herrero; M. Marcos, P. Galindo, J. M. Miralles, J. J. Corrales
      Abstract: The origin of hypogonadism, a condition including both symptoms and biochemical criteria of androgen deficiency, in type 2 diabetes is poorly known. In a cross‐sectional study of 267 unselected patients, we analyzed the potential correlation of several clinical and biochemical variables as well as chronic micro‐ and macrovascular diabetic complications with hypogonadism. Hypogonadism was present in 46 patients (17.2%) using a cutoff of total testosterone 10.4 nmol/L and in 31 (11.6%) with a cutoff of 8 nmol/L. Among these patients, hypogonadotropic hypogonadism was the most prevalent form (82.6%). Compared to eugonadal subjects, hypogonadal men had significantly lower glomerular filtration rate (67.1 ± 23.4 vs. 78.4 ± 24.6 mL/min/1.73 m2, p = 0.005) and higher prevalence of chronic kidney disease (43.5% vs. 20.4%, p = 0.002), abnormal liver function tests (26.7% vs. 12%, p = 0.019), and psychiatric treatment (23.9% vs. 10.4%, p = 0.025). Total testosterone levels correlated inversely with age (R = −0.164, p = 0.007), fasting blood glucose (R = −0.127, p = 0.037), and triglycerides (R = −0.134, p = 0.029) and directly with glomerular filtration rate (R = 0.148, p = 0.015). Calculated free testosterone and bioavailable testosterone correlated directly with hemoglobin (R = 0.171, p = 0.015 and R = 0.234, p = 0.001, respectively). Multivariate logistic regression analysis, after adjusting for relevant confounding variables, showed that age >60 years (OR = 3.58, CI 95% = 1.48–8.69, p = 0.005), body mass index >27 kg/m2 (OR = 2.85, CI 95% = 1.14–7.11, p = 0.025), hypertriglyceridemia (OR = 2.16, CI 95% = 1.05–4.41, p = 0.035), glomerular filtration rate
      PubDate: 2017-11-16T17:50:35.571-05:00
      DOI: 10.1111/andr.12433
  • Dietary patterns and semen quality: a systematic review and
           meta‐analysis of observational studies
    • Authors: A. Arab; N. Rafie, M. Mansourian, M. Miraghajani, H. Hajianfar
      Abstract: A number of studies have examined the association between dietary patterns and semen quality, but the findings have been inconclusive. Herein, we conducted a systematic review and meta‐analysis of observational studies to assess the association between dietary patterns and semen quality. PubMed, Cochrane library, Science direct, Scopus, Google Scholar, and ISI web of science databases were searched up to August 2016 for observational studies assessing the association between common dietary patterns and sperm quality markers. Data were pooled by the generic inverse variance method with random effects and expressed as mean differences with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochrane Q‐statistic) and quantified (I2‐statistic). The Newcastle‐Ottawa Scale assessed study quality. Six eligible studies, involving 8207 participants, were included in our systematic review and meta‐analysis. The pooled mean difference of sperm concentration for the healthy dietary pattern versus unhealthy dietary pattern intake was mean difference: 0.66; 95% CI, 0.305–1.016; p 
      PubDate: 2017-10-12T11:15:24.876689-05:
      DOI: 10.1111/andr.12430
  • Contributors to the substantial variation in on‐treatment testosterone
           levels in men receiving transdermal testosterone gels in randomized trials
    • Authors: S. Bhasin; T. G. Travison, L. O'Brien, J. MacKrell, V. Krishnan, H. Ouyang, K. Pencina, S. Basaria
      Abstract: There is substantial inter‐individual variability in serum testosterone levels in hypogonadal men treated with testosterone gels. We aimed to elucidate participant‐level factors that contribute to inter‐individual variability in testosterone levels during testosterone therapy. An exploratory aim was to determine whether polymorphisms in genes encoding testosterone‐metabolizing enzymes could explain the variation in on‐treatment testosterone concentrations in men who were randomized to testosterone arm in TOM Trial. We used data from three randomized trials that used 1% transdermal testosterone gels and had testosterone levels measured 2–4 weeks after randomization for dose adjustment: Testosterone in Older Men with Mobility Limitation (TOM), Effects of Testosterone on Pain Perception (TAP), and Effects of Testosterone on Atherosclerosis Progression (TEAAM). Forty‐seven percent, 38%, and 9% of participants in TAP, TEAAM, and TOM trials, respectively, failed to raise testosterone levels >400 ng/dL; 6, 8, and 30% of participants had on‐treatment testosterone levels >1000 ng/dL. Even after dose adjustment, there was substantial variation in on‐treatment levels at subsequent study visits. Baseline characteristics (age, height, weight, baseline testosterone, SHBG, hematocrit, and creatinine) accounted for only a small fraction of the variance (
      PubDate: 2017-10-05T11:25:23.621676-05:
      DOI: 10.1111/andr.12428
  • Carnitine partially improves oxidative stress, acrosome integrity, and
           reproductive competence in doxorubicin‐treated rats
    • Authors: R. E. L. Cabral; T. B. Mendes, V. Vendramini, S. M. Miraglia
      Abstract: Doxorubicin has been largely used in anticancer therapy in adults, adolescents, and children. The efficacy of l‐carnitine as an antioxidant substance has been confirmed both in humans and rats. Carnitine, present in testis and epididymis, is involved in sperm maturation. It is also effective in infertility treatment. As a continuation of a previous study, we evaluated whether some spermatic qualitative parameters, DNA integrity, chromatin structure, and fertility status, could be ameliorated by the carnitine treatment in adult rats, which were subsequently exposed to doxorubicin at pre‐puberty. Pre‐pubertal male rats were distributed into four groups: Sham Control; Doxorubicin; l‐carnitine; l‐carnitine + Doxorubicin (l‐carnitine injected 1 h before doxorubicin). At 100 days of age, all groups were reassigned into two sets: One set was submitted to the evaluation of sperm motility, acrosome integrity, mitochondrial activity, sperm chromatin structure analysis (SCSA), and evaluation of the oxidative stress. The other set of rats was destined to the evaluation of reproductive competence. The percentage of spermatozoa with intact acrosome integrity was higher in the Carnitine+Doxorubicin group when compared with the Doxorubicin group. However, sperm motility and mitochondrial activity were not improved by carnitine pre‐treatment. Both values of malondialdehyde and nitrite (indirect measurement of nitric oxide) concentrations were statistically higher in the only doxorubicin‐treated group when compared to the Carnitine + Doxorubicin group. Fertility index and implantation rate were lower in Doxorubicin group, when compared to Carnitine + Doxorubicin group. Moreover, the percentage of spermatozoa with damaged DNA was higher in the Doxorubicin‐treated group when compared to the Carnitine+Doxorubicin group. l‐carnitine, when administered before doxorubicin, partially preserved the acrosome integrity, an important feature related to sperm fertilization ability that positively correlated with the reproductive competence and sperm DNA integrity at adulthood. In conclusion, l‐carnitine attenuated the long‐term alterations caused by doxorubicin in the germ cells and improved male reproductive capacity in adulthood.
      PubDate: 2017-10-03T15:40:26.266008-05:
      DOI: 10.1111/andr.12426
  • Testosterone does not affect agrin cleavage in mobility‐limited older
           men despite improvement in physical function
    • Authors: T. Gagliano-Jucá; T. W. Storer, K. M. Pencina, T. G. Travison, Z. Li, G. Huang, S. Hettwer, P. Dahinden, S. Bhasin, S. Basaria
      Abstract: In a subset of men, sarcopenia and physical dysfunction occur due to destabilization of the neuromuscular junction (NMJ), which is manifested by elevated serum concentrations of C‐terminal agrin fragment (CAF). Testosterone administration improves physical function in some studies; however, its effects on serum circulating CAF concentrations remain unknown. Here we evaluate the effects of testosterone administration on circulating CAF levels in mobility‐limited men with low testosterone aged 65 or older participating in the Testosterone in Older Men with Mobility Limitations (TOM) Trial. We analyzed the difference in change in serum CAF levels between testosterone and placebo groups, as well as its association with muscle strength and physical function. Association of change in serum CAF levels with serum total (TT) and free testosterone (FT) was also evaluated. Men randomized to testosterone experienced significant improvement in muscle strength and physical function (assessed by loaded stair‐climbing power). However; testosterone administration was not associated with a reduction in serum CAF levels (effect size = −50.3 pm; 95% CI = −162.1 to 61.5 pm; p = 0.374); there was no association between changes in CAF levels with changes in TT (p = 0.670) or FT (p = 0.747). There was no association between changes in serum CAF levels with improvement in either muscle strength or stair‐climbing power. In conclusion, testosterone treatment in mobility‐limited older men with low to low‐normal testosterone levels did not reduce serum CAF levels. Additionally, testosterone‐induced improvements in muscle strength and physical function were not associated with changes in serum CAF concentrations. These findings suggest that improvement in physical function with testosterone replacement in older men with mobility limitations and elevated CAF levels is mediated by mechanisms other than stabilization of the NMJ.
      PubDate: 2017-09-26T16:06:18.584146-05:
      DOI: 10.1111/andr.12424
  • Effects of testosterone supplementation therapy on lipid metabolism in
           hypogonadal men with T2DM: a meta‐analysis of randomized controlled
    • Authors: K.-S. Zhang; M.-J. Zhao, Q. An, Y.-F. Jia, L.-L. Fu, J.-F. Xu, Y.-Q. Gu
      Abstract: Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta‐analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5 years, were included in this study. The pooled results of the meta‐analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of −6.44 (95% CI: −11.82 to −1.06; I2 = 28%; p = 0.02) and −27.94 (95% CI: −52.33 to −3.54; I2 = 76%; p = 0.02). Subgroup analyses revealed that the heterogeneity (I2 = 76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2 = 45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL‐C level in developing countries compared with the control group (MD = 2.79; 95% CI: 0.73 to 4.86; I2 = 0%; p = 0.008), but there was no improvement in developed countries (MD = 1.02; 95% CI: −4.55 to 6.60; I2 = 91%; p = 0.72). However, LDL‐C levels were not improved consistently. Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.
      PubDate: 2017-09-26T16:05:38.633881-05:
      DOI: 10.1111/andr.12425
  • Evaluation of sperm DNA quality in men presenting with testicular cancer
           and lymphoma using alkaline and neutral Comet assays
    • Authors: K. Kumar; S. Lewis, S. Vinci, A. Riera-Escamilla, M.-G. Fino, L. Tamburrino, M. Muratori, P. Larsen, C. Krausz
      Abstract: Despite more cancers in young men over the past two decades, improvements in therapies give a greater chance to live full lives following treatment. Sperm genomic quality is variable following cancer diagnosis, so its assessment is important if sperm cryopreservation is being considered. Here, we evaluated DNA damage using two DNA damage assays: an alkaline and for the first time, a neutral Comet assays in men presenting with testicular cancer (n = 19 for alkaline and 13 for neutral group) and lymphoma (n = 13 for alkaline and 09 for neutral group) compared with fertile donors (n = 20 for alkaline and 14 for neutral group). No significant differences were observed in any semen analysis parameters. In contrast, sperm DNA damage was higher in men with testicular cancer than in donors as assessed by both the alkaline (12.4% vs. 37.4%, p 
      PubDate: 2017-09-26T16:05:22.865652-05:
      DOI: 10.1111/andr.12429
  • Technologies of cryoprotectant‐free vitrification of human spermatozoa:
           asepticity as criterion of effectiveness
    • Authors: V. Isachenko; G. Rahimi, P. Mallmann, R. Sanchez, E. Isachenko
      First page: 1055
      Abstract: This review describes 120 years history of technology for cryoprotectant‐free cryopreservation of human spermatozoa by direct plunging into liquid nitrogen (vitrification). It is presented an explanation why cryoprotectant‐free vitrification for some human ejaculates is better than conventional freezing and vitrification with the presence of cryoprotectants. Special attention is given to the extremely high viability of viruses, bacteria and micoplasmas after cryoprotectant‐free cryopreservation in culture medium and even in distilled water. This fact increases the potential risk of disease transmission through liquid nitrogen. It is concretized the concept “asepticity” as obvious parameter for any medical assisted reproduction technology which includes the cooling of cells in liquid nitrogen. It is described the role of nonpermeable compounds of mediums for cryoprotectant‐free vitrification: carbohydrates, proteins, lipoproteins, antioxidants. This review summarizes concerned data regarding two groups of different current technologies for cryoprotectant‐free vitrification of human spermatozoa: with direct contact of spermatozoa with liquid nitrogen as well as with full isolation of these cells from liquid nitrogen (aseptic technologies).
      PubDate: 2017-10-09T12:05:21.092846-05:
      DOI: 10.1111/andr.12414
  • Male accessory gland inflammation, infertility, and sexual dysfunctions: a
           practical approach to diagnosis and therapy
    • Authors: A. E. Calogero; Y. Duca, R. A. Condorelli, S. La Vignera
      First page: 1064
      Abstract: The role of urogenital inflammation in causing infertility and sexual dysfunctions has long been a matter of debate in the international scientific literature. The most recent scientific evidences show that male accessory gland infection/inflammation could alter, with various mechanisms, both conventional and biofunctional sperm parameters, and determine worst reproductive outcome. At the same time, the high prevalence of erectile dysfunction and premature ejaculation in patients with male accessory gland infection/inflammation underlines the close link between these diseases and sexual dysfunctions. The aim of this review was to provide the reader the basis for a correct diagnosis of male accessory gland infection/inflammation and a subsequent appropriate therapeutic approach, particularly in patients with infertility and/or sexual dysfunction.
      PubDate: 2017-10-09T12:10:22.978222-05:
      DOI: 10.1111/andr.12427
  • Altered brain networks in psychogenic erectile dysfunction: a
           resting‐state fMRI study
    • Authors: J. Chen; Y. Chen, G. Chen, Y. Dai, Z. Yao, Q. Lu
      First page: 1073
      Abstract: Various neuroimaging studies had identified changes of cerebral activity and structures during the processes of sexual arousal. The identified brain regions were also believed to regulate emotional and cognitive processes. Yet, little was known about the neural mechanisms underlying psychogenic erectile dysfunction. Moreover, brain mechanisms mediating the processing of sexual arousal by these psychological processes were unclear. To investigate this issue, graph theory was applied to evaluate the topological properties of functional brain networks among 24 psychogenic erectile dysfunction patients and 26 healthy controls. Abnormal metrics and correlations with clinical characteristics were further analyzed. Our results showed that psychogenic erectile dysfunction had higher small‐worldness and more modules. Furthermore, psychogenic erectile dysfunction showed altered path length and strength of the right superior frontal gyrus (dorsolateral), superior parietal gyrus, parahippocampal gyrus and left temporal pole (superior temporal gyrus), post‐central gyrus, mainly located in the cognitive control and emotional regulation subnetworks. And the altered parameters of the small‐worldness and right parahippocampal gyrus were related to the clinical characteristics of psychogenic erectile dysfunction. Together, our results suggested that psychogenic erectile dysfunction was associated with disruptions in the topological structure of functional brain subnetworks underlying the cognitive and emotional processes.
      PubDate: 2017-10-26T14:20:33.70834-05:0
      DOI: 10.1111/andr.12411
  • Male urinary paracetamol and semen quality
    • Authors: M. M. Smarr; K. Kannan, Z. Chen, S. Kim, G. M. Buck Louis
      First page: 1082
      Abstract: The endocrine-disrupting properties of paracetamol have been previously demonstrated in rodent studies of abnormal sperm morphology and diminished testosterone production, in addition to epidemiologic studies of diminished couple fecundity. In this study, we examined the relationship between paracetamol and its metabolite p-aminophenol quantified in a single spot urine and semen quality among 501 male partners of couples planning for pregnancy. Men provided a urine specimen and two fresh semen samples collected approximately one month apart and underwent 24-h analysis for 35 semen quality parameters. Paracetamol and p-aminophenol were quantified in urine by ultra-high-performance liquid chromatography coupled with an electrospray triple quadrupole mass spectrometry. The relationship between natural-log-transformed urinary paracetamol and p-aminophenol rescaled by their standard deviation and 21 Box-Cox-transformed, 14 non-transformed semen parameters was assessed using linear mixed-effects models. The median concentrations (IQR) of urinary paracetamol and p-aminophenol were 15.5 ng/mL (5.44, 73.5) and 978 ng/mL (500, 1596), respectively. Following adjustment for creatinine and age, a 1-standard deviation increase in log-transformed urinary paracetamol was associated with a reduction in beat cross-frequency and an increase in DNA fragmentation [β (95% CI): −0.59 Hz (−1.16, −0.03) and 0.05% (0.01, 0.09), respectively]. These findings were corroborated in models of categorical chemical concentrations; higher concentrations of paracetamol remained associated with reduced beat cross-frequency and increased DNA fragmentation. A 1-standard deviation increase in log-transformed urinary p-aminophenol was associated with a reduction in sperm head area [β (95% CI): −0.1 μm2 (−0.18, −0.02) and width −0.02 μm (−0.04, −0.01)]. However, only the association with sperm head area remained statistically significant in models of p-aminophenol quartiles. Our findings suggest that adult male urinary paracetamol is associated with sperm motility and DNA fragmentation, while the metabolite, p-aminophenol, is predominantly associated with sperm head morphometry.
      PubDate: 2017-08-29T10:55:19.482547-05:
      DOI: 10.1111/andr.12413
  • Cigarette smoking significantly alters sperm DNA methylation patterns
    • Authors: T. G. Jenkins; E. R. James, D. F. Alonso, J. R. Hoidal, P. J. Murphy, J. M. Hotaling, B. R. Cairns, D. T. Carrell, K. I. Aston
      First page: 1089
      Abstract: Numerous health consequences of tobacco smoke exposure have been characterized, and the effects of smoking on traditional measures of male fertility are well described. However, a growing body of data indicates that pre‐conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through spermatozoa. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never‐smokers using the Infinium Human Methylation 450 beadchip. We investigated two models of DNA methylation alterations: (i) consistently altered methylation at specific CpGs or within specific genomic regions and (ii) stochastic DNA methylation alterations manifest as increased variability in genome‐wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome‐wide in sperm DNA from men who smoke compared with never‐smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre‐conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.
      PubDate: 2017-09-26T15:55:33.069698-05:
      DOI: 10.1111/andr.12416
  • Predictive value of pre‐operative inflammation‐based prognostic scores
           (neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and
           monocyte‐to‐eosinophil ratio) in testicular sperm extraction: a pilot
    • Authors: C. Yucel; M. Z. Keskin, O. Cakmak, B. Ergani, C. Kose, O. Celik, E. Islamoglu, M. Ucar, G. Koc, Z. Kozacioglu
      First page: 1100
      Abstract: To investigate the ability of some hematologic prognostic scores demonstrating inflammation in predicting sperm presence in testicular sperm extraction (TESE). We retrospectively investigated the medical data of 430 patients with the diagnosis of non‐obstruc tive azoospermia (NOA) who had undergone TESE operation consecutively in our institution between the dates of January 2009 and February 2017. In all, 352 patients with the diagnosis of NOA, with bilaterally palpable vas deferens, who had undergone TESE for the first time, were included in the study. Patients with genetic anomalies, genital infection, history of surgery or vasectomy, chronic diseases, history of inflammatory, metabolic, rheumatologic, or malignant diseases, morbid obesity, with the diagnosis of clinical varicocele, or patients who had undergone TESE for the second time were excluded from the study. According to the results of TESE, the patients were divided into two groups as those with sperm retrieval and those without sperm retrieval. These groups were compared in terms of age, infertility duration, body mass index, hormone profile, hematologic parameters, neutrophil‐to‐lymphocyte ratio (NRL), monocyte‐to‐eosinophil ratio (MER), and platelet‐to‐lymphocyte ratio (PLR). The NLR and PLR levels were found to be significantly higher in patients without sperm retrieval at TESE compared to those with sperm retrieval. The logistic regression analysis showed NLR as an independent factor that showed the presence of spermatozoa at TESE (odds ratio: 4.786, %95 confidence interval: 2.667–8.589, p 
      PubDate: 2017-10-09T12:05:24.680666-05:
      DOI: 10.1111/andr.12417
  • Possible involvement of the glucocorticoid receptor (NR3C1) and selected
           NR3C1 gene variants in regulation of human testicular function
    • Authors: L. Nordkap; K. Almstrup, J. E. Nielsen, A. K. Bang, L. Priskorn, M. Krause, S. A. Holmboe, S. B. Winge, D. L. Egeberg Palme, N. Mørup, J. H. Petersen, A. Juul, N. E. Skakkebæk, E. Rajpert-De Meyts, N. Jørgensen
      First page: 1105
      Abstract: Perceived stress has been associated with decreased semen quality but the mechanisms have not been elucidated. It is not known whether cortisol, the major stress hormone in humans, can act directly via receptors in the testis, and whether variants in the gene encoding the glucocorticoid receptor (NR3C1) can possibly modulate the effect. To address these questions, we investigated the expression of the glucocorticoid receptor in human testicular tissue, including adult and fetal samples (n = 20) by immunohistochemical staining, and in silico analysis of publicly available datasets. In the adult testis NR3C1 protein was detected in peritubular cells, a subset of Leydig cells, Sertoli cells (weak), and spermatogonia, but not in spermatids. The NR3C1 expression pattern in fetal testis samples differed by a notably stronger reaction in Sertoli cells, lack of staining in gonocytes but the presence in a subset of pro‐spermatogonia, and the almost absent reaction in nascent peritubular cells. In parallel, we explored the association between adult testicular function and three single nucleotide NR3C1 polymorphisms (BcII [rs41423247], 9β [rs6198], and Tth111I [rs10052957]) affecting glucocorticoid sensitivity. Testicular function was determined by semen analysis and reproductive hormone profiling in 893 men from the general population. The NR3C1 SNP BclI was associated with semen quality in an over‐dominant manner with heterozygotes having better semen parameters compared to both homozygote constellations, and with sperm motility showing the strongest association. This association was supported by a higher inhibin B and inhibin B/FSH ratio, as well as a lower FSH in BclI heterozygotes. The SNPs 9β and Tth111I were not associated with semen parameters. Although the clinical impact of the findings is limited, the results substantiate a suggested link between stress and testicular function. Hence this investigation should be regarded as a discovery study generating hypotheses for future studies.
      PubDate: 2017-10-09T12:05:48.357716-05:
      DOI: 10.1111/andr.12418
  • Isotretinoin administration improves sperm production in men with
           infertility from oligoasthenozoospermia: a pilot study
    • Authors: J. K. Amory; K. A. Ostrowski, J. R. Gannon, K. Berkseth, F. Stevison, N. Isoherranen, C. H. Muller, T. Walsh
      First page: 1115
      Abstract: There is currently no effective medical therapy for men with infertility due to oligoasthenozoospermia. As men with abnormal sperm production have lower concentrations of 13‐cis‐retinoic acid in their testes, we hypothesized that men with infertility from oligoasthenozoospermia might have improved sperm counts when treated with isotretinoin (13‐cis‐retinoic acid). We conducted a single‐site, single‐arm, pilot study to determine the effect of therapy with isotretinoin on sperm indices in 19 infertile men with oligoasthenozoospermia. Subjects were men between 21 and 60 years of age with infertility for longer than 12 months associated with sperm concentrations below 15 million sperm/mL. All men received isotretinoin 20 mg by mouth twice daily for 20 weeks. Subjects had semen analyses, physical examinations, and laboratory tests every 4 weeks during treatment. Nineteen men enrolled in the study. Median (25th, 75th) sperm concentration increased from 2.5 (0.1, 5.9) million/mL at baseline to 3.8 (2.1, 13.0) million/mL at the end of treatment (p = 0.006). No significant changes in sperm motility were observed. There was a trend toward improved sperm morphology (p = 0.056). Six pregnancies (three spontaneous and three from intracytoplasmic sperm injection) and five births occurred during the study. Four of the births, including all three of the spontaneous pregnancies, were observed in men with improvements in sperm counts with isotretinoin therapy. Treatment was well tolerated. Isotretinoin therapy improves sperm production in some men with oligoasthenozoospermia. Additional studies of isotretinoin in men with infertility from oligoasthenozoospermia are warranted.
      PubDate: 2017-10-05T01:30:02.484085-05:
      DOI: 10.1111/andr.12420
  • Paternal age and risk of testicular germ cell tumors: a cohort study of
           1,000,000 men
    • Authors: H. Levine; L. Keinan-Boker, A. Leiba, E. Derazne, A. Rais, J. D. Kark
      First page: 1124
      Abstract: Testicular germ cell tumors (TGCT) are the most frequent cancer among young men, with increasing incidence worldwide. Advanced paternal age has been linked to adverse health outcomes in offspring, but reports on the association of paternal age with TGCT are few and inconsistent. We aimed to examine the relationship of paternal age (PAB) at birth with the risk of TGCT and by histologic type: seminoma and non‐seminoma. A population‐based cohort of 1,056,058 males, examined at ages 16–19 between the years 1980–2011, was linked to the Israel National Cancer Registry to obtain incident TGCT through 2012. We applied multivariable Cox regression. During 16.5 million person‐years of follow‐up, 1247 incident cases (604 seminomas and 643 non‐seminomas) were detected. Increasing PAB was linearly associated with lower risk of TGCT (HRper year = 0.983, 95% CI: 0.974–0.993, p = 0.001), after adjustment for year of birth, years of education, height, cryptorchidism history and origin, and also with additional adjustment for maternal age at birth (MAB) (HRper year = 0.980: 0.965–0.995, p = 0.008). The association was stronger for seminoma (HRper year = 0.968: 0.946–0.989, p = 0.004) and persisted in a subset adjusted for sibship size (HRper year = 0.950: 0.917–0.983, p = 0.003). In the fully adjusted model, young PAB (15–24 vs. ≥30) was a risk factor for seminoma (HR = 1.41: 1.07–1.85, p = 0.014). In models adjusted for PAB, MAB was not associated with risk of TGCT. In conclusion, our findings suggest that young paternal age is a risk factor of TGCT, especially seminoma. The findings warrant further investigation into the possible impact of young paternal age on their offsprings’ testes.
      PubDate: 2017-09-26T16:00:23.075021-05:
      DOI: 10.1111/andr.12422
  • Human sperm motility is downregulated by the AMPK activator A769662
    • Authors: V. Calle-Guisado; A. Hurtado de Llera, L. González-Fernández, M. J. Bragado, L. J. Garcia-Marin
      First page: 1131
      Abstract: AMP‐activated kinase (AMPK) plays a key function in maintaining cellular energy homeostasis. We recently identified and localized AMPK protein in human spermatozoa and showed that inhibition of AMPK activity significantly modified human sperm motility. Recently, AMPK has gained great relevance as prime target for pharmacological approaches in several energy‐related pathologies and therefore pharmacological research is aimed to develop direct AMPK‐activating compounds such as A769662. Our aim was to investigate the effect of A769662 in essential functional processes of human spermatozoa. Human spermatozoa were incubated in the presence or absence of the AMPK activator A769662 for different incubation times (0–20 h) and motility was evaluated by CASA system whereas other functional parameters were evaluated by flow cytometry. A769662 treatment significantly reduces the percentages of motile, progressive, and rapid spermatozoa starting at 2 h. Moreover, AMPK activator in human spermatozoa causes a significant reduction in any velocity measured, which is concomitant to a significant decrease in the percentage of rapid spermatozoa, both at short‐ (2–3 h) and long‐time treatment (20 h). Treatment of human spermatozoa with A769662 does not significantly alter any of the following functional parameters: sperm viability, mitochondrial membrane potential, phosphatidylserine translocation to the outer leaf of plasma membrane, acrosome membrane integrity, or mitochondrial superoxide anion production. In summary, our results suggest that AMPK in human spermatozoa contributes to the regulation of sperm motility, without affecting basic physiological parameters of human spermatozoa (viability, mitochondrial membrane potential or reactive oxygen species production, acrosome membrane integrity, phosphatidylserine exposure at plasma membrane). As sperm motility is required in the female reproductive tract to achieve fertilization, we conclude that AMPK is an essential regulatory kinase of the human spermatozoa function. This conclusion needs to be taken into account when AMPK is elected as prime target in pharmacological approaches for several energy‐related pathologies.
      PubDate: 2017-10-05T01:30:03.575137-05:
      DOI: 10.1111/andr.12423
  • Spontaneous testicular atrophy occurs despite normal spermatogonial
           proliferation in a Tp53 knockout rat
    • Authors: M. S. Dai; S. J. Hall, M. M. Vantangoli Policelli, K. Boekelheide, D. J. Spade
      First page: 1141
      Abstract: The tumor suppressor protein p53 (TP53) has many functions in cell cycle regulation, apoptosis, and DNA damage repair and is also involved in spermatogenesis in the mouse. To evaluate the role of p53 in spermatogenesis in the rat, we characterized testis biology in adult males of a novel p53 knockout rat (SD-Tp53tm1sage). p53 knockout rats exhibited variable levels of testicular atrophy, including significantly decreased testis weights, atrophic seminiferous tubules, decreased seminiferous tubule diameter, and elevated spermatocyte TUNEL labeling rates, indicating a dysfunction in spermatogenesis. Phosphorylated histone H2AX protein levels and distribution were similar in the non-atrophic seminiferous tubules of both genotypes, showing evidence of pre-synaptic DNA double-strand breaks in leptotene and zygotene spermatocytes, preceding cell death in p53 knockout rat testes. Quantification of the spermatogonial stem cell (SSC) proliferation rate with bromodeoxyuridine (BrdU) labeling, in addition to staining with the undifferentiated type A spermatogonial marker GDNF family receptor alpha-1 (GFRA1), indicated that the undifferentiated spermatogonial population was normal in p53 knockout rats. Following exposure to 0.5 or 5 Gy X-ray, p53 knockout rats exhibited no germ cell apoptotic response beyond their unirradiated phenotype, while germ cell death in wild-type rat testes was elevated to a level similar to the unexposed p53 knockout rats. This study indicates that seminiferous tubule atrophy occurs following spontaneous, elevated levels of spermatocyte death in the p53 knockout rat. This phenomenon is variable across individual rats. These results indicate a critical role for p53 in rat germ cell survival and spermatogenesis.
      PubDate: 2017-08-22T17:21:07.304319-05:
      DOI: 10.1111/andr.12409
  • Relationship of aquaporins 3 (AQP3), 7 (AQP7), and 11 (AQP11) with boar
           sperm resilience to withstand freeze–thawing procedures
    • Authors: N. Prieto-Martínez; I. Vilagran, R. Morató, M. M. Rivera del Álamo, J. E. Rodríguez-Gil, S. Bonet, M. Yeste
      First page: 1153
      Abstract: Cryopreservation is the most suitable method to preserve boar spermatozoa over long‐term storage. However, freeze–thawing protocols inflict extensive damage to sperm cells, reducing their viability and compromising their fertilizing ability. In addition, high individual variability is known to exist between boar ejaculates, which may be classified as of good (GFE) or poor (PFE) freezability. While conventional spermiogram parameters fail to predict sperm cryotolerance in fresh spermatozoa, high levels of certain proteins, also known as freezability markers, have been found to be related to the sperm resilience to withstand freeze–thawing procedures. In this context, the hypothesis of this study was that aquaporins AQP3, AQP7, and AQP11 could be linked to boar sperm cryotolerance. Twenty‐nine ejaculates were evaluated and subsequently classified as GFE or PFE based upon their sperm viability and motility at post‐thawing. Fourteen ejaculates resulted to be GFE, whereas the other fifteen were found to be PFE. Relative abundances of AQP3, AQP7, and AQP11 and their localization patterns were evaluated in all fresh and frozen–thawed ejaculates through immunoblotting and immunocytochemistry. Prior to cryopreservation, relative amounts of AQP3 and AQP7 were found to be significantly (p  0.05) between freezability groups were found for AQP11, despite GFE tending to present higher levels of this protein. The localization of AQP7, but not that of AQP3 or AQP11, was observed to be affected by cryopreservation procedures. In conclusion, these results suggest that AQP3 and AQP7 are related to boar sperm cryotolerance and may be used as freezability markers.
      PubDate: 2017-09-21T12:25:51.116713-05:
      DOI: 10.1111/andr.12410
  • Transdifferentiation of adult rat stem Leydig cells into prostatic and
           uterine epithelium, but not epidermis
    • Authors: M. K. Nanjappa; T. I. Medrano, G. S. Prins, H. Chen, B. R. Zirkin, P. S. Cooke
      First page: 1165
      Abstract: Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete testosterone required for male sexual differentiation, spermatogenesis, and fertility, were recently identified in rat testes. Various types of stem cells have shown the ability to differentiate into other tissues, but there is no information on the plasticity of adult rat SLCs (rSLCs). This study investigated the ability of rSLCs to transdifferentiate into cell types from all three germ layers—prostatic epithelium (endoderm), uterine epithelium (mesoderm), and epidermis (ectoderm)—under the influence of inductive mesenchyme from fetal and neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme from green fluorescent protein (GFP)‐expressing mice was used. Tissue recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs grafted into adult male hosts formed ductal structures resembling prostate after 5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP expression, and expressed characteristic markers of prostatic epithelium. Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple columnar epithelium that was histologically similar to normal uterine epithelium and expressed typical uterine epithelial markers, but was of rSLC origin. In contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants, suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate into uterine and prostatic epithelium, mesodermal, and endodermal derivatives, respectively, but they may have a limited transdifferentiation potential, as shown by their inability to form epidermis, an ectodermal derivative.
      PubDate: 2017-10-26T14:21:13.709759-05:
      DOI: 10.1111/andr.12415
  • Stallion spermatozoa surviving freezing and thawing experience membrane
           depolarization and increased intracellular Na+
    • Authors: C. Ortega Ferrusola; L. Anel-López, J. M. Ortiz-Rodriguez, P. Martin Muñoz, M. Alvarez, P. Paz, J. Masot, E. Redondo, C. Balao da Silva, J. M. Morrell, H. Rodriguez Martinez, J. A. Tapia, M. C. Gil, L. Anel, F. J. Peña
      First page: 1174
      Abstract: In order to gain insight of the modifications that freezing and thawing cause to the surviving population of spermatozoa, changes in the potential of the plasma membrane (Em) and intracellular Na+ content of stallion spermatozoa were investigated using flow cytometry. Moreover, caspase 3 activity was also investigated and the functionality of the Na+‐K+ ATPase pump was investigated before and after freezing and thawing. Cryopreservation caused a significant (p 
      PubDate: 2017-10-03T15:25:51.294084-05:
      DOI: 10.1111/andr.12419
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