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Publisher: Oxford University Press   (Total: 406 journals)

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Showing 1 - 200 of 406 Journals sorted alphabetically
ACS Symposium Series     Full-text available via subscription   (Followers: 1, SJR: 0.189, CiteScore: 0)
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Adaptation     Hybrid Journal   (Followers: 9, SJR: 0.143, CiteScore: 0)
Advances in Nutrition     Hybrid Journal   (Followers: 54, SJR: 2.196, CiteScore: 5)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.434, CiteScore: 1)
Aesthetic Surgery J. Open Forum     Open Access  
African Affairs     Hybrid Journal   (Followers: 66, SJR: 1.869, CiteScore: 2)
Age and Ageing     Hybrid Journal   (Followers: 90, SJR: 1.989, CiteScore: 4)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 18, SJR: 1.376, CiteScore: 3)
American Entomologist     Full-text available via subscription   (Followers: 8)
American Historical Review     Hybrid Journal   (Followers: 179, SJR: 0.467, CiteScore: 1)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 2.113, CiteScore: 3)
American J. of Clinical Nutrition     Hybrid Journal   (Followers: 187, SJR: 3.438, CiteScore: 6)
American J. of Epidemiology     Hybrid Journal   (Followers: 196, SJR: 2.713, CiteScore: 3)
American J. of Health-System Pharmacy     Full-text available via subscription   (Followers: 55, SJR: 0.595, CiteScore: 1)
American J. of Hypertension     Hybrid Journal   (Followers: 26, SJR: 1.322, CiteScore: 3)
American J. of Jurisprudence     Hybrid Journal   (Followers: 19, SJR: 0.281, CiteScore: 1)
American J. of Legal History     Full-text available via subscription   (Followers: 9, SJR: 0.116, CiteScore: 0)
American Law and Economics Review     Hybrid Journal   (Followers: 28, SJR: 1.053, CiteScore: 1)
American Literary History     Hybrid Journal   (Followers: 17, SJR: 0.391, CiteScore: 0)
Analysis     Hybrid Journal   (Followers: 23, SJR: 1.038, CiteScore: 1)
Animal Frontiers     Hybrid Journal   (Followers: 1)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 16, SJR: 1.423, CiteScore: 3)
Annals of Botany     Hybrid Journal   (Followers: 38, SJR: 1.721, CiteScore: 4)
Annals of Oncology     Hybrid Journal   (Followers: 55, SJR: 5.599, CiteScore: 9)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 11, SJR: 0.722, CiteScore: 1)
Annals of Work Exposures and Health     Hybrid Journal   (Followers: 34, SJR: 0.728, CiteScore: 2)
Antibody Therapeutics     Open Access  
AoB Plants     Open Access   (Followers: 4, SJR: 1.28, CiteScore: 3)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 17, SJR: 0.858, CiteScore: 2)
Applied Linguistics     Hybrid Journal   (Followers: 60, SJR: 2.987, CiteScore: 3)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 1.241, CiteScore: 1)
Arbitration Intl.     Full-text available via subscription   (Followers: 21)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 14)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 30, SJR: 0.731, CiteScore: 2)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 3)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 44, SJR: 0.146, CiteScore: 0)
Behavioral Ecology     Hybrid Journal   (Followers: 53, SJR: 1.871, CiteScore: 3)
Bioinformatics     Hybrid Journal   (Followers: 348, SJR: 6.14, CiteScore: 8)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 10, SJR: 1.446, CiteScore: 3)
Biometrika     Hybrid Journal   (Followers: 20, SJR: 3.485, CiteScore: 2)
BioScience     Hybrid Journal   (Followers: 29, SJR: 2.754, CiteScore: 4)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 2, SJR: 0.146, CiteScore: 0)
Biostatistics     Hybrid Journal   (Followers: 17, SJR: 1.553, CiteScore: 2)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 189, SJR: 2.115, CiteScore: 3)
BJA Education     Hybrid Journal   (Followers: 66)
Brain     Hybrid Journal   (Followers: 70, SJR: 5.858, CiteScore: 7)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 49, SJR: 2.505, CiteScore: 5)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 3, SJR: 2.15, CiteScore: 3)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 38, SJR: 2.161, CiteScore: 2)
British J. of Aesthetics     Hybrid Journal   (Followers: 25, SJR: 0.508, CiteScore: 1)
British J. of Criminology     Hybrid Journal   (Followers: 603, SJR: 1.828, CiteScore: 3)
British J. of Social Work     Hybrid Journal   (Followers: 86, SJR: 1.019, CiteScore: 2)
British Medical Bulletin     Hybrid Journal   (Followers: 6, SJR: 1.355, CiteScore: 3)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 35)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 4, SJR: 1.376, CiteScore: 1)
Cambridge J. of Economics     Hybrid Journal   (Followers: 71, SJR: 0.764, CiteScore: 2)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 12, SJR: 2.438, CiteScore: 4)
Cambridge Quarterly     Hybrid Journal   (Followers: 10, SJR: 0.104, CiteScore: 0)
Capital Markets Law J.     Hybrid Journal   (Followers: 2, SJR: 0.222, CiteScore: 0)
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.135, CiteScore: 5)
Cardiovascular Research     Hybrid Journal   (Followers: 14, SJR: 3.002, CiteScore: 5)
Cerebral Cortex     Hybrid Journal   (Followers: 52, SJR: 3.892, CiteScore: 6)
CESifo Economic Studies     Hybrid Journal   (Followers: 23, SJR: 0.483, CiteScore: 1)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.42, CiteScore: 3)
Children and Schools     Hybrid Journal   (Followers: 6, SJR: 0.246, CiteScore: 0)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 5, SJR: 0.412, CiteScore: 0)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 23, SJR: 0.329, CiteScore: 0)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 10, SJR: 1.392, CiteScore: 2)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 10, SJR: 0.183, CiteScore: 0)
Classical Receptions J.     Hybrid Journal   (Followers: 27, SJR: 0.123, CiteScore: 0)
Clean Energy     Open Access   (Followers: 1)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 70, SJR: 5.051, CiteScore: 5)
Communication Theory     Hybrid Journal   (Followers: 25, SJR: 2.424, CiteScore: 3)
Communication, Culture & Critique     Hybrid Journal   (Followers: 28, SJR: 0.222, CiteScore: 1)
Community Development J.     Hybrid Journal   (Followers: 27, SJR: 0.268, CiteScore: 1)
Computer J.     Hybrid Journal   (Followers: 9, SJR: 0.319, CiteScore: 1)
Conservation Physiology     Open Access   (Followers: 3, SJR: 1.818, CiteScore: 3)
Contemporary Women's Writing     Hybrid Journal   (Followers: 9, SJR: 0.121, CiteScore: 0)
Contributions to Political Economy     Hybrid Journal   (Followers: 6, SJR: 0.906, CiteScore: 1)
Critical Values     Full-text available via subscription  
Current Developments in Nutrition     Open Access   (Followers: 3)
Current Legal Problems     Hybrid Journal   (Followers: 29)
Current Zoology     Full-text available via subscription   (Followers: 3, SJR: 1.164, CiteScore: 2)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 9, SJR: 1.791, CiteScore: 3)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 14, SJR: 0.259, CiteScore: 1)
Diplomatic History     Hybrid Journal   (Followers: 21, SJR: 0.45, CiteScore: 1)
DNA Research     Open Access   (Followers: 5, SJR: 2.866, CiteScore: 6)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 4)
Early Music     Hybrid Journal   (Followers: 17, SJR: 0.139, CiteScore: 0)
Econometrics J.     Hybrid Journal   (Followers: 32, SJR: 2.926, CiteScore: 1)
Economic J.     Hybrid Journal   (Followers: 116, SJR: 5.161, CiteScore: 3)
Economic Policy     Hybrid Journal   (Followers: 48, SJR: 3.584, CiteScore: 3)
ELT J.     Hybrid Journal   (Followers: 24, SJR: 0.942, CiteScore: 1)
English Historical Review     Hybrid Journal   (Followers: 56, SJR: 0.612, CiteScore: 1)
English: J. of the English Association     Hybrid Journal   (Followers: 18, SJR: 0.1, CiteScore: 0)
Environmental Entomology     Full-text available via subscription   (Followers: 11, SJR: 0.818, CiteScore: 2)
Environmental Epigenetics     Open Access   (Followers: 2)
Environmental History     Hybrid Journal   (Followers: 26, SJR: 0.408, CiteScore: 1)
EP-Europace     Hybrid Journal   (Followers: 3, SJR: 2.748, CiteScore: 4)
Epidemiologic Reviews     Hybrid Journal   (Followers: 9, SJR: 4.505, CiteScore: 8)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 20, SJR: 0.113, CiteScore: 0)
European Heart J.     Hybrid Journal   (Followers: 66, SJR: 9.315, CiteScore: 9)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 10, SJR: 3.625, CiteScore: 3)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 2)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. : Case Reports     Open Access  
European Heart J. Supplements     Hybrid Journal   (Followers: 8, SJR: 0.223, CiteScore: 0)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 9, SJR: 1.681, CiteScore: 2)
European J. of Intl. Law     Hybrid Journal   (Followers: 206, SJR: 0.694, CiteScore: 1)
European J. of Orthodontics     Hybrid Journal   (Followers: 5, SJR: 1.279, CiteScore: 2)
European J. of Public Health     Hybrid Journal   (Followers: 19, SJR: 1.36, CiteScore: 2)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 10, SJR: 1.172, CiteScore: 2)
European Review of Economic History     Hybrid Journal   (Followers: 30, SJR: 0.702, CiteScore: 1)
European Sociological Review     Hybrid Journal   (Followers: 43, SJR: 2.728, CiteScore: 3)
Evolution, Medicine, and Public Health     Open Access   (Followers: 12)
Family Practice     Hybrid Journal   (Followers: 15, SJR: 1.018, CiteScore: 2)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 16, SJR: 1.492, CiteScore: 4)
Fems Microbiology Letters     Hybrid Journal   (Followers: 28, SJR: 0.79, CiteScore: 2)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 33, SJR: 7.063, CiteScore: 13)
Fems Yeast Research     Hybrid Journal   (Followers: 14, SJR: 1.308, CiteScore: 3)
Food Quality and Safety     Open Access   (Followers: 1)
Foreign Policy Analysis     Hybrid Journal   (Followers: 24, SJR: 1.425, CiteScore: 1)
Forest Science     Hybrid Journal   (Followers: 8, SJR: 0.89, CiteScore: 2)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 16, SJR: 1.133, CiteScore: 3)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.104, CiteScore: 0)
French History     Hybrid Journal   (Followers: 34, SJR: 0.118, CiteScore: 0)
French Studies     Hybrid Journal   (Followers: 21, SJR: 0.148, CiteScore: 0)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.152, CiteScore: 0)
Gastroenterology Report     Open Access   (Followers: 3)
Genome Biology and Evolution     Open Access   (Followers: 16, SJR: 2.578, CiteScore: 4)
Geophysical J. Intl.     Hybrid Journal   (Followers: 39, SJR: 1.506, CiteScore: 3)
German History     Hybrid Journal   (Followers: 23, SJR: 0.161, CiteScore: 0)
GigaScience     Open Access   (Followers: 6, SJR: 5.022, CiteScore: 7)
Global Summitry     Hybrid Journal   (Followers: 1)
Glycobiology     Hybrid Journal   (Followers: 13, SJR: 1.493, CiteScore: 3)
Health and Social Work     Hybrid Journal   (Followers: 57, SJR: 0.388, CiteScore: 1)
Health Education Research     Hybrid Journal   (Followers: 15, SJR: 0.854, CiteScore: 2)
Health Policy and Planning     Hybrid Journal   (Followers: 24, SJR: 1.512, CiteScore: 2)
Health Promotion Intl.     Hybrid Journal   (Followers: 22, SJR: 0.812, CiteScore: 2)
History Workshop J.     Hybrid Journal   (Followers: 33, SJR: 1.278, CiteScore: 1)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 28, SJR: 0.105, CiteScore: 0)
Human Communication Research     Hybrid Journal   (Followers: 15, SJR: 2.146, CiteScore: 3)
Human Molecular Genetics     Hybrid Journal   (Followers: 9, SJR: 3.555, CiteScore: 5)
Human Reproduction     Hybrid Journal   (Followers: 75, SJR: 2.643, CiteScore: 5)
Human Reproduction Open     Open Access   (Followers: 1)
Human Reproduction Update     Hybrid Journal   (Followers: 21, SJR: 5.317, CiteScore: 10)
Human Rights Law Review     Hybrid Journal   (Followers: 64, SJR: 0.756, CiteScore: 1)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 58, SJR: 1.591, CiteScore: 3)
ICSID Review : Foreign Investment Law J.     Hybrid Journal   (Followers: 11)
ILAR J.     Hybrid Journal   (Followers: 3, SJR: 1.732, CiteScore: 4)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.679, CiteScore: 1)
IMA J. of Management Mathematics     Hybrid Journal   (SJR: 0.538, CiteScore: 1)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.496, CiteScore: 1)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 1.987, CiteScore: 2)
Industrial and Corporate Change     Hybrid Journal   (Followers: 10, SJR: 1.792, CiteScore: 2)
Industrial Law J.     Hybrid Journal   (Followers: 41, SJR: 0.249, CiteScore: 1)
Inflammatory Bowel Diseases     Hybrid Journal   (Followers: 47, SJR: 2.511, CiteScore: 4)
Information and Inference     Free  
Innovation in Aging     Open Access  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 9, SJR: 1.319, CiteScore: 2)
Integrative Biology     Full-text available via subscription   (Followers: 6, SJR: 1.36, CiteScore: 3)
Integrative Organismal Biology     Open Access  
Interacting with Computers     Hybrid Journal   (Followers: 11, SJR: 0.292, CiteScore: 1)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 7, SJR: 0.762, CiteScore: 1)
Intl. Affairs     Hybrid Journal   (Followers: 68, SJR: 1.505, CiteScore: 3)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 27)
Intl. Health     Hybrid Journal   (Followers: 6, SJR: 0.851, CiteScore: 2)
Intl. Immunology     Hybrid Journal   (Followers: 3, SJR: 2.167, CiteScore: 4)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 36, SJR: 1.348, CiteScore: 2)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 65, SJR: 0.601, CiteScore: 1)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 261, SJR: 3.969, CiteScore: 5)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 5, SJR: 0.202, CiteScore: 1)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 28, SJR: 0.223, CiteScore: 1)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 10, SJR: 0.285, CiteScore: 1)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.403, CiteScore: 1)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 3, SJR: 1.808, CiteScore: 4)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 11, SJR: 1.545, CiteScore: 1)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 39, SJR: 0.389, CiteScore: 1)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 11, SJR: 0.724, CiteScore: 2)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.168, CiteScore: 1)
Intl. Political Sociology     Hybrid Journal   (Followers: 40, SJR: 1.465, CiteScore: 3)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 24, SJR: 0.401, CiteScore: 1)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 9, SJR: 0.983, CiteScore: 1)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 50, SJR: 2.581, CiteScore: 2)
Intl. Studies Review     Hybrid Journal   (Followers: 25, SJR: 1.201, CiteScore: 1)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 2, SJR: 0.15, CiteScore: 0)
ITNOW     Hybrid Journal   (Followers: 1, SJR: 0.103, CiteScore: 0)
J. of African Economies     Hybrid Journal   (Followers: 17, SJR: 0.533, CiteScore: 1)
J. of American History     Hybrid Journal   (Followers: 46, SJR: 0.297, CiteScore: 1)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 14, SJR: 1.065, CiteScore: 2)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 15, SJR: 2.419, CiteScore: 4)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 5, SJR: 0.585, CiteScore: 1)
J. of Biochemistry     Hybrid Journal   (Followers: 41, SJR: 1.226, CiteScore: 2)
J. of Breast Imaging     Full-text available via subscription   (Followers: 1)
J. of Burn Care & Research     Hybrid Journal   (Followers: 11, SJR: 0.768, CiteScore: 2)

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Similar Journals
Journal Cover
Biology of Reproduction
Journal Prestige (SJR): 1.446
Citation Impact (citeScore): 3
Number of Followers: 10  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0006-3363 - ISSN (Online) 1529-7268
Published by Oxford University Press Homepage  [406 journals]
  • Dual role of TGF-β in early pregnancy: clues from tumor progression
    • Authors: Latifi Z; Nejabati H, Abroon S, et al.
      Pages: 1417 - 1430
      Abstract: TGF-β signaling in the endometrium is active during the implantation period and has a pivotal role in regulating endometrial receptivity and embryo implantation. During embryo implantation, both apoptosis and proliferation of endometrial cells happen at the same time and it seems TGF-β is the factor that controls both of these processes. As shown in cancer cells, in special conditions this cytokine can have a dual effect and switch the action from apoptosis to proliferation. Owing to the similarity between embryo implantation and cancer development and also unusual pattern of proliferation and remodeling in the uterus, in this review we suggest the existence of such a switching in endometrium during the early pregnancy. Moreover, we address some potential mechanisms that could regulate the switching. A better understanding of the molecular mechanisms regulating TGF-β action and signaling during the implantation period could pave the way for introducing novel therapeutic strategies in order to solve implantation-associated issues such as repeated implantation failure.
      PubDate: Sun, 17 Feb 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz024
      Issue No: Vol. 100, No. 6 (2019)
       
  • Endo-siRNAs regulate early embryonic development by inhibiting
           transcription of long terminal repeat sequence in pig†
    • Authors: Kong Q; Quan X, Du J, et al.
      Pages: 1431 - 1439
      Abstract: Activity of some endogenous retroviruses (ERVs) has been proven to be important for development of early mammalian embryo. However, abnormal activation of ERVs can also cause genetic diseases due to their ability to retrotranspose, so the regulatory mechanism to limit transcription of ERVs needs to be clarified. Endogenous small interfering RNA (endo-siRNA) has been reported to protect cells against transposable elements (TEs). Here, we determined the role of ERVs long terminal repeat sequences (LTRs) derived endo-siRNAs (LTR-siRNAs) on inhibition of the activity of ERVs during early embryonic development in pig. Seven most highly expressed LTR-siRNAs were identified in porcine zygote by high-throughput small RNA sequencing. We verified that the biogenesis of the LTR-siRNAs was DICER-dependent and they were generated from double-stranded RNA (dsRNA) formed by sense and antisense transcripts of LTRs. And, the expression of sense and antisense of LTRs might be due to the loss of DNA methylation at some LTR loci. Furthermore, we showed that the LTR-siRNAs could regulate early embryonic development by repression of LTRs expression at a post-transcriptional level. So, we propose here, during early embryonic development when epigenetic reprogramming occurs, the endo-siRNA pathway acts as a sophisticated balance of regulatory mechanism for ERV activity.
      PubDate: Mon, 18 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz042
      Issue No: Vol. 100, No. 6 (2019)
       
  • Comprehensive evaluation of ubiquitous promoters suitable for the
           generation of transgenic cynomolgus monkeys†
    • Authors: Seita Y; Tsukiyama T, Azami T, et al.
      Pages: 1440 - 1452
      Abstract: Nonhuman primates (NHPs) are considered to be the most valuable models for human transgenic (Tg) research into disease because human pathology is more closely recapitulated in NHPs than rodents. Previous studies have reported the generation of Tg NHPs that ubiquitously overexpress a transgene using various promoters, but it is not yet clear which promoter is most suitable for the generation of NHPs overexpressing a transgene ubiquitously and persistently in various tissues. To clarify this issue, we evaluated four putative ubiquitous promoters, cytomegalovirus (CMV) immediate-early enhancer and chicken beta-actin (CAG), elongation factor 1α (EF1α), ubiquitin C (UbC), and CMV, using an in vitro differentiation system of cynomolgus monkey embryonic stem cells (ESCs). While the EF1α promoter drove Tg expression more strongly than the other promoters in undifferentiated pluripotent ESCs, the CAG promoter was more effective in differentiated cells such as embryoid bodies and ESC-derived neurons. When the CAG and EF1α promoters were used to generate green fluorescent protein (GFP)-expressing Tg monkeys, the CAG promoter drove GFP expression in skin and hematopoietic tissues more strongly than in ΕF1α-GFP Tg monkeys. Notably, the EF1α promoter underwent more silencing in both ESCs and Tg monkeys. Thus, the CAG promoter appears to be the most suitable for ubiquitous and stable expression of transgenes in the differentiated tissues of Tg cynomolgus monkeys and appropriate for the establishment of human disease models.
      PubDate: Thu, 14 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz040
      Issue No: Vol. 100, No. 6 (2019)
       
  • Endometrial cells contribute to preexisting endometriosis lesions in a
           mouse model of retrograde menstruation†
    • Authors: Tal A; Tal R, Pluchino N, et al.
      Pages: 1453 - 1460
      Abstract: Endometriosis is characterized by extrauterine growth of endometrial tissue accompanied by adverse clinical manifestations including chronic pelvic pain and infertility. Retrograde menstruation, the efflux of endometrium into the peritoneal cavity during menstruation, is believed to contribute to implantation of endometrial tissue and formation of endometriotic lesions at ectopic sites. While it is established through various rodent and nonhuman primate models that endometrial tissue fragments, as well as nondissociated stroma and glands, are capable of seeding endometriosis in a manner mimicking retrograde menstruation, the ability of single endometrial cells to participate in endometriotic processes has not been evaluated due to their failure to establish macroscopic endometriosis. We designed a model by which this capacity can be assessed by examining the integration of individual uterine cells into existing endometriosis lesions in mice. Endometriosis was induced in C57BL/6J female mice followed by intraperitoneal injection of GFP-labeled single uterine cells. We found that freshly introduced uterine cells can successfully integrate and contribute to various cell populations within the lesion. Strikingly, these cells also appeared to contribute to neo-angiogenesis and inflammatory processes within the lesion, which are commonly thought of as host-driven phenomena. Our findings underscore the potential of individual uterine cells to continuously expand lesions and participate in the progression of endometriosis. This model of retrograde menstruation may therefore be used to study processes involved in the pathophysiology of endometriosis.
      PubDate: Thu, 14 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz039
      Issue No: Vol. 100, No. 6 (2019)
       
  • The perforatorium and postacrosomal sheath of rat spermatozoa share common
           developmental origins and protein constituents†
    • Authors: Protopapas N; Hamilton L, Warkentin R, et al.
      Pages: 1461 - 1472
      Abstract: The perinuclear theca (PT) is a cytosolic protein capsule that surrounds the nucleus of eutherian spermatozoa. Compositionally, it is divided into two regions: the subacrosomal layer (SAL) and the postacrosomal sheath (PAS). In falciform spermatozoa, a third region of the PT emerges that extends beyond the nuclear apex called the perforatorium. The formation of the SAL and PAS differs, with the former assembling early in spermiogenesis concomitant with acrosome formation, and the latter dependent on manchette descent during spermatid elongation. The perforatorium also forms during the elongation phase of spermiogenesis, suggesting that like the PAS, its assembly is facilitated by the manchette. The temporal similarity in biogenesis between the PAS and perforatorium led us to compare their molecular composition using cell fractionation and immunodetection techniques. Although the perforatorium is predominantly composed of its endemic protein FABP9/PERF15, immunolocalization indicates that it also shares proteins with the PAS. These include WBP2NL/PAWP, WBP2, GSTO2, and core histones, which have been implicated in early fertilization and zygotic events. The compositional homogeny between the PAS and perforatorium supports our observation that their development is linked. Immunocytochemistry indicates that both PAS and perforatorial biogenesis depend on the transport and deposition of cytosolic proteins by the microtubular manchette. Proteins translocated from the manchette pass ventrally along the spermatid head into the apical perforatorial space prior to PAS deposition in the wake of manchette descent. Our findings demonstrate that the perforatorium and PAS share a mechanism of developmental assembly and thereby contain common proteins that facilitate fertilization.
      PubDate: Tue, 02 Apr 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz052
      Issue No: Vol. 100, No. 6 (2019)
       
  • Plasminogen activator, tissue type regulates germinal vesicle breakdown
           and cumulus expansion of bovine cumulus–oocyte complex in vitro†
    • Authors: Yu B; Subudeng G, Du C, et al.
      Pages: 1473 - 1481
      Abstract: Plasminogen activator, tissue type (PLAT) and its inhibitor serpin family E member 1 (SERPINE1) cooperatively regulate PLAT activity in various reproductive processes. However, it is unknown whether this includes bovine oocyte maturation. We addressed this question in the present study by evaluating PLAT and SERPINE1 protein localization in immature cumulus–oocyte complexes (COCs), as well as PLAT mRNA and protein expression in cultured COCs after 0, 8, 16, and 24 h of in vitro maturation (IVM). We also examined the effects of PLAT and SERPINE1 on germinal vesicle breakdown (GVBD) and oocyte cyclic 3' 5' adenosine monophosphate (cAMP) levels, cumulus expansion index, and expansion-related gene expression in oocytes derived from bovine COCs cultured for 4, 8, and 12 h and in COCs cultured for 16 h. Both PLAT and SERPINE1 localized in cumulus cells but only the latter was detected in oocytes. PLAT and SERPINE1 transcript levels increased during IVM; however, from 8 to 16 h, the levels of PLAT remained stable whereas those of SERPINE1 increased, resulting in a decline in PLAT concentration. Additionally, PLAT delayed GVBD, increased oocyte cAMP levels, and blocked cumulus expansion and associated gene expression, which was reversed by SERPINE1 supplemented. Thus, PLAT delays bovine oocyte GVBD by enhancing oocyte cAMP levels during the first 8 h of IVM; suppression of PLAT activity via accumulation of SERPINE1 in COCs results in cumulus expansion from 8 to 16 h of IVM. These findings provide novel insights into the molecular mechanisms underlying in vitro bovine oocyte maturation.
      PubDate: Tue, 02 Apr 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz049
      Issue No: Vol. 100, No. 6 (2019)
       
  • Membrane raft-mediated regulation of glucose signaling pathway leading to
           acrosome reaction in chicken sperm†
    • Authors: Ushiyama A; Priyadarshana C, Setiawan R, et al.
      Pages: 1482 - 1491
      Abstract: Despite knowledge that glucose metabolism is essential for the regulation of signaling cascades in the sperm that are pre-assembled into specific areas and function at multistage for fertilization, the physiological roles of glucose in avian sperm are poorly understood. Accumulated results of studies conducted in our laboratory and others indicate that sperm possess membrane microdomains, or membrane rafts, which play important roles in several processes, including the induction of acrosome reaction (AR). When characterizing proteomes associated with chicken sperm rafts, we observed marked enrichment of glucose transporter 3 (GLUT3). Here we show that glucose uptake is mediated by membrane rafts and stimulates AR induction by activating AMP-activated protein kinase (AMPK). Using a specific antibody, we observed that GLUT3 is localized to the entire flagellum and acrosome region and highly associated with membrane rafts. The addition of glucose stimulated AR in a dose-dependent manner without affecting sperm motility. AR and glucose uptake assays were performed using both inhibitors and activators, and demonstrated that glucose-dependent AR results from the activity of a glucose transporter located in membrane rafts and associated with AMPK. To better understand the mechanism of AMPK activation by glucose, we evaluated localization and phosphorylation status of AMPKα, showing that glucose uptake stimulates AMPKα phosphorylation, leading to its complete activation. Together, these results lead us to propose a novel mechanism by which glucose uptake stimulates the AMPK signaling pathway via membrane rafts, resulting in maximal acrosomal responsiveness in avian sperm as migrating upward to a fertilization site.
      PubDate: Mon, 04 Feb 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz015
      Issue No: Vol. 100, No. 6 (2019)
       
  • Autoimmune Regulator is required in female mice for optimal embryonic
           development and implantation†
    • Authors: Warren B; Ahn S, McGinnis L, et al.
      Pages: 1492 - 1504
      Abstract: Autoimmune Regulator (AIRE) regulates central immune tolerance by inducing expression of tissue-restricted antigens in thymic medullary epithelial cells, thereby ensuring elimination of autoreactive T cells. Aire mutations in humans and targeted Aire deletion in mice result in multiorgan autoimmune disease, known in humans as autoimmune polyglandular syndrome type 1 (APS-1). APS-1 is characterized by the presence of adrenal insufficiency, chronic mucosal candidiasis, and/or hypoparathyroidism. Additionally, females often present with gonadal insufficiency and infertility. Aire-deficiency (KO) in mice results in oophoritis and age-dependent depletion of follicular reserves. Here, we found that while the majority of young 6-week-old Aire-KO females had normal follicular reserves, mating behavior, and ovulation rates, 50% of females experienced embryonic loss between gestation day (GD) 5.5 and 7.5 that could not be attributed to insufficient progesterone production or decidualization. The quality of GD0.5 embryos recovered from Aire KO mice was reduced, and when cultured in vitro, embryos displayed limited developmental capacity in comparison to those recovered from wild-type (WT) mice. Further, embryos flushed from Aire KO dams at GD3.5 were developmentally delayed in comparison to WT controls and had reduced trophoblastic outgrowth in vitro. We conclude that AIRE does not play a direct role in uterine decidualization. Rather, reduced fertility of Aire-deficient females is likely due to multiple factors, including oophoritis, delayed preimplantation development, and compromised implantation. These effects may be explained by autoimmune targeting of the ovary, embryo, or both. Alternatively, altered embryonic development could be due to a direct role for AIRE in early embryogenesis.
      PubDate: Sat, 16 Feb 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz023
      Issue No: Vol. 100, No. 6 (2019)
       
  • Molecular machinery providing copper bioavailability for spermatozoa along
           the epididymial tubule in mouse
    • Authors: Ogórek M; Herman S, Pierzchała O, et al.
      Pages: 1505 - 1520
      Abstract: Progressive functional maturation of spermatozoa is completed during the transit of these cells through the epididymis, a tubule structure connecting a testicle to a vas deferens. Epididymal epithelial cells by means of their secretory and absorptive functions determine a highly specialized luminal microenvironment containing multiple organic and inorganic components. The latter include copper ions, which due to their redox properties are indispensable for critical homeostatic processes occurring in spermatozoa floating in different part of epididymis but can be potentially toxic. Main purpose of our study was to determine epididymal region-dependent expression and localization of copper transporters ensuring a tight control of copper concentration in epididymal fluid. We also aimed at identifying proteins responsible for copper uptake by spermatozoa and verifying whether this process is coordinated with copper supply to superoxide dismutase 1 (SOD1), a copper-dependent antioxidant enzyme. Our study identifies two ATPases—ATP7A, ATP7B and Slc31a1, major copper importers/exporters depending on their differential expression on epididymal polarized epithelial cells of the caput, corpus, and cauda. Next, ceruloplasmin seems to be a chief protein transporting copper in the epididymal fluid and providing this biometal to spermatozoa. The entry of copper to germ cells is mediated by Slc31a1 and is correlated with both expressions of copper chaperone for superoxide dismutase (CCS), copper chaperone directly providing copper ions to SOD1 and with the expression and activity of the latter. Our results outline a network of cooperating copper binding proteins expressed in epididymal epithelium and in spermatozoa that orchestrate bioavailability of this microelement for gametes and protect them against copper toxicity.
      PubDate: Tue, 19 Feb 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz028
      Issue No: Vol. 100, No. 6 (2019)
       
  • Human recombinant FSH induces chemoresistance in human breast cancer cells
           via HIF-1α activation†
    • Authors: Bergandi L; Canosa S, Pittatore G, et al.
      Pages: 1521 - 1535
      Abstract: Breast cancer patients under 40 years of age who are candidate to chemotherapy with alkylating drugs may undergo controlled ovarian stimulation (COS) with recombinant human follicle-stimulating hormone (rhFSH) in order to get fertility preservation by mature oocyte cryostorage. The direct effect(s) of exogenous rhFSH on the chemosensitivity of breast cancer is currently unknown. To clarify this issue, we incubated four different breast cancer cell lines with rhFSH (10 IU/L, 24 h) and then we exposed them to doxorubicin (DOX) or cyclophosphamide (CPA). The effect(s) of rhFSH on human breast cancer cells treated with DOX or CPA was measured in terms of (1) cell viability, (2) cytotoxicity, (3) multidrug resistance (MDR) genes and proteins expression and activities, and (4) hypoxia-inducible factor 1-alpha (HIF-1α) activation. Pretreatment with rhFSH significantly increased the viability of breast cancer cells after treatment with DOX or CPA, and reduced the lactate dehydrogenase leakage and reactive oxygen species production. Moreover, after preincubation with rhFSH, the MDR proteins (Pgp, MPR1, and BCRP) expression and activity resulted upregulated and the HIF-1α pathway activated. In addition, the use of a widely used HIF-1α inhibitor, the 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), prevented the rhFSH effect on the onset of MDR. Taken together, these observations suggest that a short exposure to rhFSH induces chemoresistance to DOX and CPA in human breast cancer cells via HIF-1α activation.
      PubDate: Tue, 02 Apr 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz050
      Issue No: Vol. 100, No. 6 (2019)
       
  • MiR-664-2 impacts pubertal development in a precocious-puberty rat model
           through targeting the NMDA receptor-1†
    • Authors: Ju M; Yang L, Zhu J, et al.
      Pages: 1536 - 1548
      Abstract: Precocious puberty (PP) commonly results from premature activation of the hypothalamic–pituitary–gonadal axis (HPGA). Gonadotropin-releasing hormone (GnRH) is the initial trigger for HPGA activation and plays an important role in puberty onset. N-methyl-D-aspartate (NMDA) can promote pulsatile GnRH secretion and accelerates puberty onset. However, the mechanism of N-methyl-D-aspartate receptors (NMDARs) in PP pathogenesis remains obscure. We found that serum GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen (E2) levels, hypothalamic NMDAR1, and GnRH mRNA expression peaked at the vaginal opening (VO) day. Next, the hypothalamic NMDAR1 mRNA and protein levels in rats treated with danazol, a chemical commonly effecting on the reproductive system, were significantly increased at the VO day (postnatal day 24) compared to controls, accompanied by enhanced serum GnRH, LH, FSH, and E2 levels. Further, microRNA-664-2 (miR-664-2) was selected after bioinformatics analysis and approved in primary hypothalamic neurons, which binds to the 3′-untranslated regions of NMDAR1. Consistently, the miR-664-2 expression in hypothalamus of the Danazol group was decreased compared to Vehicle. Our results suggested that attenuated miR-664-2 might participate in PP pathogenesis through enhancing the NMDAR1 signaling.
      PubDate: Wed, 27 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz044
      Issue No: Vol. 100, No. 6 (2019)
       
  • Hyperprolactinemic African elephant (Loxodonta africana) females exhibit
           elevated dopamine, oxytocin and serotonin concentrations compared to
           normal cycling and noncycling, low prolactin elephants†
    • Authors: Prado N; Keady M, Oestmann A, et al.
      Pages: 1549 - 1560
      Abstract: Many zoo elephants do not cycle normally, and for African elephants, it is often associated with hyperprolactinemia. Dopamine agonists successfully treat hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n = 7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n = 13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n = 8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented.
      PubDate: Fri, 08 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz036
      Issue No: Vol. 100, No. 6 (2019)
       
  • Prenatal exposure to di-(2-ethylhexyl) phthalate and high-fat diet
           synergistically disrupts mouse fetal oogenesis and affects
           folliculogenesis†
    • Authors: Mirihagalle S; You T, Suh L, et al.
      Pages: 1561 - 1570
      Abstract: Di-(2-ethylhexyl) phthalate (DEHP) is a chemical that is widely used as a plasticizer. Exposure to DEHP has been shown to alter ovarian function in humans. Additionally, foods high in fat content, regularly found in the western diet, have been shown to be another potential disruptor of fetal ovarian function. Due to DEHP’s lipophilicity, high-fat foods can be easily contaminated. Therefore, exposure to DEHP and a high-fat diet are both health concerns, especially in pregnant women, and the effects of these exposures on fetal oocyte quality and quantity should be elucidated. In this study, our goal was to determine if there are synergistic effects of DEHP exposure at an environmentally relevant level (20 μg/kg body weight/day) and high-fat diet on oogenesis and folliculogenesis. Dams were fed with a high-fat diet (45 kcal% fat) or a control diet (10 kcal% fat) 1 week before mating and during pregnancy and lactation. The pregnant mice were dosed with DEHP (20 μg/kg body weight/day) or vehicle control from E10.5 to litter birth. We found that treatment with an environmentally relevant dosage of DEHP and consumption of high-fat diet significantly increases synapsis defects in meiosis and affects folliculogenesis in the F1 generation.
      PubDate: Tue, 02 Apr 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz051
      Issue No: Vol. 100, No. 6 (2019)
       
  • Progesterone receptor membrane component 1 and 2 regulate granulosa cell
           mitosis and survival through a NFΚB-dependent mechanism†
    • Authors: Peluso J; Pru C, Liu X, et al.
      Pages: 1571 - 1580
      Abstract: Progesterone receptor membrane component 1 (PGRMC1) interacts with PGRMC2, and disrupting this interaction in spontaneously immortalized granulosa cells (SIGCS) leads to an inappropriate entry into the cell cycle, mitotic arrest, and ultimately cell death. The present study revealed that PGRMC1 and PGRMC2 localize to the cytoplasm of murine granulosa cells of nonatretric follicles with their staining intensity being somewhat diminished in granulosa cells of atretic follicles. Compared to controls (Pgrmc1fl/fl), the rate at which granulosa cells entered the cell cycle increased in nonatretic and atretic follicles of mice in which Pgrmc1 was conditionally deleted (Pgrmc1d/d) from granulosa cells. This increased rate of entry into the cell cycle was associated with a ≥ 2-fold increase in follicular atresia and the nuclear localization of nuclear factor-kappa-B transcription factor P65; (NFΚB/p65, or RELA). GTPase activating protein binding protein 2 (G3BP2) binds NFΚB/p65 through an interaction with NFΚB inhibitor alpha (IκBα), thereby maintaining NFΚB/p65’s cytoplasmic localization and restricting its transcriptional activity. Since PGRMC1 and PGRMC2 bind G3BP2, studies were designed to assess the functional relationship between PGRMC1, PGRMC2, and NFΚB/p65 in SIGCs. In these studies, disrupting the interaction between PGRMC1 and PGRMC2 increased the nuclear localization of NFΚB/p65, and depleting PGRMC1, PGRMC2, or G3BP2 increased NFΚB transcriptional activity and the progression into the cell cycle. Taken together, these studies suggest that PGRMC1 and 2 regulate granulosa cell cycle entry in follicles by precisely controlling the localization and thereby the transcriptional activity of NFΚB/p65.
      PubDate: Sat, 16 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz043
      Issue No: Vol. 100, No. 6 (2019)
       
  • Molecular profiling demonstrates modulation of immune cell function and
           matrix remodeling during luteal rescue†
    • Authors: Hughes C; Maalouf S, Liu W, et al.
      Pages: 1581 - 1596
      Abstract: The corpus luteum (CL) is essential for maintenance of pregnancy in all mammals and luteal rescue, which occurs around day 16–19 in the cow, is necessary to maintain luteal progesterone production. Transcriptomic and proteomic profiling were performed to compare the day 17 bovine CL of the estrous cycle and pregnancy. Among mRNA and proteins measured, 140 differentially abundant mRNA and 24 differentially abundant proteins were identified. Pathway analysis was performed using four programs. Modulated pathways included T cell receptor signaling, vascular stability, cytokine signaling, and extracellular matrix remodeling. Two mRNA that were less in pregnancy were regulated by prostaglandin F2A in culture, while two mRNA that were greater in pregnancy were regulated by interferon tau. To identify mRNA that could be critical regulators of luteal fate, the mRNA that were differentially abundant during early pregnancy were compared to mRNA that were differentially abundant during luteal regression. Eight mRNA were common to both datasets, including mRNA related to regulation of steroidogenesis and gene transcription. A subset of differentially abundant mRNA and proteins, including those associated with extracellular matrix functions, were predicted targets of differentially abundant microRNA (miRNA). Integration of miRNA and protein data, using miRPath, revealed pathways such as extracellular matrix–receptor interactions, abundance of glutathione, and cellular metabolism and energy balance. Overall, this study has provided a comprehensive profile of molecular changes in the corpus luteum during maternal recognition of pregnancy and has indicated that some of these functions may be miRNA-regulated.
      PubDate: Wed, 27 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz037
      Issue No: Vol. 100, No. 6 (2019)
       
  • Matrix metalloproteinases 2 and 9 are elevated in human preterm laboring
           uterine myometrium and exacerbate uterine contractility†
    • Authors: Ulrich C; Arinze V, Wandscheer C, et al.
      Pages: 1597 - 1604
      Abstract: Matrix metalloproteinases 2 and 9 (MMP2/9) have previously been shown to be elevated in serum and amniotic fluid from women undergoing preterm birth. We performed experiments to determine the effects of MMP2/9 on uterine contraction and birth timing. Pregnant mice were injected daily with 50 mg/kg of SB-3CT or vehicle control beginning on gestational day 14–18 to determine if MMP2/9 inhibition would affect parturition timing. MMP2/9 expression in human myometrial tissue was determined by Simple Western (Wes) and semiquantitative western blot. Purified MMP2/9 and SB-3CT inhibitor were added to human myometrial strips to determine the effects of MMP2/9 on oxytocin-induced uterine contraction. Parturition was delayed in mice treated with MMP2/9 inhibitor SB-3CT. MMP2/9 protein levels were elevated in preterm laboring uterine myometrium. Gelatinase activity was confirmed in cell extracts and supernatants from immortalized and primary human uterine myometrial cells in culture. Addition of purified MMP2/9 increased the oxytocin-induced contractile response in myometrial tissue strips from pregnant women. In contrast, addition of the MMP2/9 inhibitor SB-3CT decreased the contractile response to oxytocin in a dose-dependent manner. These results suggest abnormal MMP2/9 expression affects the contractile state of the uterine myometrium to promote parturition and that MMP2/9 inhibition attenuates this effect.
      PubDate: Fri, 05 Apr 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz054
      Issue No: Vol. 100, No. 6 (2019)
       
  • Dexamethasone induces primary amnion epithelial cell senescence through
           telomere-P21 associated pathway†
    • Authors: Martin L; Richardson L, da Silva M, et al.
      Pages: 1605 - 1616
      Abstract: Dexamethasone (Dex), a corticosteroid hormone, is used during the perinatal period to help fetal lung and other organ development. Conversely, Dex-induced cell proliferation has been associated with accelerated aging. Using primary amnion epithelial cells (AECs) from term, not in labor, fetal membranes, we tested the effects of Dex on cell proliferation, senescence, and inflammation. Primary AECs treated with Dex (100 and 200 nM) for 48 h were tested for cell viability (crystal violet dye exclusion), cell cycle progression and/or type of cell death (flow cytometry), expression patterns of steroid receptors (glucocorticoid receptor, progesterone receptor membrane component 1&2), inflammatory mediators (IL-6 and IL-8), and telomere length (quantitative RT-PCR). Mechanistic mediators of senescence (p38MAPK and p21) were determined by western blot analysis. Dex treatment did not induce AEC proliferation, cell cycle, influence viability, or morphology. However, Dex caused dependent telomere length reduction and p38MAPK-independent but p21-dependent (confirmed by treatment with p21 inhibitor UC2288). Senescence was not associated with an increase in inflammatory mediators, which is often associated with senescence. Co-treatment with RU486 produced DNA damage, cell cycle arrest, and cellular necrosis with an increase in inflammatory mediators. The effect of Dex was devoid of changes to steroid receptors, whereas RU486 increased GR expression. Dex treatment of AECs produced nonreplicative and noninflammatory senescence. Extensive use of Dex during the perinatal period may lead to cellular senescence, contributing to cellular aging associated pathologies during the perinatal and neonatal periods.
      PubDate: Sat, 30 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz048
      Issue No: Vol. 100, No. 6 (2019)
       
  • GIT2 deficiency attenuates inflammation-induced expression of pro-labor
           mediators in human amnion and myometrial cells†
    • Authors: Lim R; Lappas M.
      Pages: 1617 - 1629
      Abstract: Untimely activation of the inflammatory response by sterile or infective insults in uterine tissues can result in preterm birth. Pro-inflammatory cytokines and pathogenic activation of toll-like receptors (TLRs) initiate a biochemical cascade of events leading to myometrial activation and contractility, cervical dilatation, and rupture of the chorioamniotic membranes. GIT2 is a signaling protein known to play a role in innate and adaptive immunity; however, its role in the inflammatory pathways of human labor is not known. In this article, we report that GIT2 expression is lower in human myometrium and fetal membranes with term labor, and in preterm amnion with histological chorioamnionitis. GIT2 knockdown by siRNA in primary myometrial and amnion cells exhibited reduced expression of pro-inflammatory cytokines and chemokines in response to inflammatory challenge by cytokines or TLR ligands. In addition, the pro-inflammatory cytokines IL1B and TNF could not induce the expression of extracellular matrix degrading enzymes in GIT2-deficient amnion cells. Myometrial activation in response to pro-inflammatory cytokines was also significantly suppressed in GIT2-deficient cells as evidenced by decreased prostaglandin release and expression of contraction-associated proteins. Further to this, collagen gel assays demonstrated that TNF had a reduced ability to induce myometrial contractility in situ in GIT2-deficient myometrial cells compared to control-transfected cells. In summary, the loss of GIT2 diminishes the effects inflammatory mediators have in promoting myometrial contraction and fetal membrane rupture in vitro, suggesting that GIT2 could be a possible target for preterm birth therapies.
      PubDate: Wed, 27 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz041
      Issue No: Vol. 100, No. 6 (2019)
       
  • Ovine uterine artery hydrogen sulfide biosynthesis in vivo: effects of
           ovarian cycle and pregnancy†
    • Authors: Lechuga T; Qi Q, Magness R, et al.
      Pages: 1630 - 1636
      Abstract: Uterine vasodilation dramatically increases during the follicular phase of the estrous cycle and pregnancy, which are estrogen-dominant physiological states. Uterine vasodilation is believed to be mainly controlled by local uterine artery (UA) production of vasodilators and angiogenic factors. The extremely potent vasodilator and proangiogenic hydrogen sulfide (H2S) is synthesized via metabolizing L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). This study was designed to determine if UA H2S production increases with augmented expression and/or activity of CBS and/or CTH during the ovarian cycle and pregnancy in sheep. Uterine arteries from intact nonpregnant (NP) luteal and follicular phase and late (130–135 days, term ≈ 145 days) pregnant (P) ewes were collected; endothelium-enriched proteins (UAendo) and endothelium-denuded smooth muscle (UAvsm) were mechanically prepared for accessing CBS and CTH proteins by immunoblotting; their cellular localization was determined by semi-quantitative immunofluorescence microscopy. H2S production was measured by the methylene blue assay. Immunoblotting revealed that CBS but not CTH protein was greater in P > > > NP follicular > luteal UAendo and UAvsm (P < 0.001). H2S production was greater in P > > > NP UAendo and UAvsm (P < 0.01). Pregnancy-augmented UAendo and UAvsm H2S production was inhibited by the specific CBS but not CTH inhibitor. CBS and CTH proteins were localized to both endothelium and smooth muscle; however, only CBS protein was significantly greater in P vs NP UA endothelium and smooth muscle. Thus, ovine UA H2S production is significantly augmented via selectively upregulating endothelium and smooth muscle CBS during the follicular phase and pregnancy in vivo.
      PubDate: Sun, 17 Feb 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz027
      Issue No: Vol. 100, No. 6 (2019)
       
  • Specific visualization of live type A spermatogonia of Pacific bluefin
           tuna using fluorescent dye-conjugated antibodies†
    • Authors: Ichida K; Kawamura W, Miwa M, et al.
      Pages: 1637 - 1647
      Abstract: During our previous work toward establishing surrogate broodstock that can produce donor-derived gametes by germ cell transplantation, we found that only type A spermatogonia (ASGs) have the potency to colonize recipient gonads. Therefore, the ability to visualize ASGs specifically would allow the sequential analysis of donor cell behavior in the recipient gonads. Here we produced monoclonal antibodies that could recognize the cell surface antigens of ASGs in Pacific bluefin tuna (Thunnus orientalis), with the aim of visualizing live ASGs. We generated monoclonal antibodies by inoculating Pacific bluefin tuna testicular cells containing ASGs into mice and then screened them using cell-based enzyme-linked immunosorbent assay (ELISA), immunocytochemistry, flow cytometry (FCM), and immunohistochemistry, which resulted in the selection of two antibodies (Nos. 152 and 180) from a pool of 1152 antibodies. We directly labeled these antibodies with fluorescent dye, which allowed ASG-like cells to be visualized in a one-step procedure using immunocytochemistry. Molecular marker analyses against the FCM-sorted fluorescent cells confirmed that ASGs were highly enriched in the antibody-positive fraction. To evaluate the migratory capability of the ASGs, we transplanted visualized cells into the peritoneal cavity of nibe croaker (Nibea mitsukurii) larvae. This resulted in incorporated fluorescent cells labeled with antibody No. 152 being detected in the recipient gonads, suggesting that the visualized ASGs possessed migratory and incorporation capabilities. Thus, the donor germ cell visualization method that was developed in this study will facilitate and simplify Pacific bluefin tuna germ cell transplantation.
      PubDate: Mon, 01 Apr 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz047
      Issue No: Vol. 100, No. 6 (2019)
       
  • Formation of organotypic testicular organoids in microwell culture†
    • Authors: Sakib S; Uchida A, Valenzuela-Leon P, et al.
      Pages: 1648 - 1660
      Abstract: Three-dimensional (3D) organoids can serve as an in vitro platform to study cell–cell interactions, tissue development, and toxicology. Development of organoids with tissue architecture similar to testis in vivo has remained a challenge. Here, we present a microwell aggregation approach to establish multicellular 3D testicular organoids from pig, mouse, macaque, and human. The organoids consist of germ cells, Sertoli cells, Leydig cells, and peritubular myoid cells forming a distinct seminiferous epithelium and interstitial compartment separated by a basement membrane. Sertoli cells in the organoids express tight junction proteins claudin 11 and occludin. Germ cells in organoids showed an attenuated response to retinoic acid compared to germ cells in 2D culture indicating that the tissue architecture of the organoid modulates response to retinoic acid similar to in vivo. Germ cells maintaining physiological cell–cell interactions in organoids also had lower levels of autophagy indicating lower levels of cellular stress. When organoids were treated with mono(2-ethylhexyl) phthalate (MEHP), levels of germ cell autophagy increased in a dose-dependent manner, indicating the utility of the organoids for toxicity screening. Ablation of primary cilia on testicular somatic cells inhibited the formation of organoids demonstrating an application to screen for factors affecting testicular morphogenesis. Organoids can be generated from cryopreserved testis cells and preserved by vitrification. Taken together, the testicular organoid system recapitulates the 3D organization of the mammalian testis and provides an in vitro platform for studying germ cell function, testicular development, and drug toxicity in a cellular context representative of the testis in vivo.
      PubDate: Sat, 30 Mar 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz053
      Issue No: Vol. 100, No. 6 (2019)
       
  • The genomic distribution of histone H3K4me2 in spermatogonia is highly
           conserved in sperm†
    • Authors: Lambrot R; Siklenka K, Lafleur C, et al.
      Pages: 1661 - 1672
      Abstract: Environmental exposures can alter the long-term health and development of offspring. How this environmental information is transmitted via the germline remains unknown, but it is thought to involve epigenetic inheritance. We recently determined that genetic disruption of histone H3 di-methylation at lysine 4 (H3K4me2) in sperm alters gene expression in the embryo and negatively impacts development across generations. However, little is known regarding when in spermatogenesis H3K4me2 methylation is established, and whether specific regions bearing H3K4me2 resist the epigenome remodeling that occurs throughout spermatogenesis. Our objective was to determine what genomic regions bearing histone H3K4me2 in spermatogonia are also present in sperm. Methods: Using transgenic mice expressing Oct4-GFP, we isolated an enriched spermatogonia population and performed ChIP-seq for H3K4me2, followed by downstream bioinformatics analysis. Using our epigenomic data and existing datasets, we compared the genomic distribution of H3K4me2 between spermatogonia and sperm. We also assessed the expression level of genes enriched in H3K4me2 in spermatogenic cell types and at specific embryonic developmental time-points. We observed that many regions of the sperm epigenome bearing H3K4me2 are already present in spermatogonia, suggesting an early establishment of this histone mark in spermatogenesis. Subsets of genes with a high enrichment in H3K4me2 in sperm are strongly expressed in spermatogenesis and others are associated with high gene expression during embryo development. These findings suggest that if epimutations in H3K4me2 are induced in spermatogonia they have the possibility to persist throughout spermatogenesis and may influence fertility by altering gene expression in spermatogenesis and in the embryo.
      PubDate: Fri, 05 Apr 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz055
      Issue No: Vol. 100, No. 6 (2019)
       
  • Non-canonical RNA polyadenylation polymerase FAM46C is essential for
           fastening sperm head and flagellum in mice†
    • Authors: Zheng C; Ouyang Y, Jiang B, et al.
      Pages: 1673 - 1685
      Abstract: Family with sequence similarity 46, member C (FAM46C) is a highly conserved non-canonical RNA polyadenylation polymerase that is abundantly expressed in human and mouse testes and is frequently mutated in patients with multiple myeloma. However, its physiological role remains largely unknown. In this study, we found that FAM46C is specifically localized to the manchette of spermatids in mouse testes, a transient microtubule-based structure mainly involved in nuclear shaping and intra-flagellar protein traffic. Gene knockout of FAM46C in mice resulted in male sterility, characterized by the production of headless spermatozoa in testes. Sperm heads were intermittently found in the epididymides of FAM46C knockout mice, but their fertilization ability was severely compromised based on the results of intracytoplasmic sperm injection assays. Interestingly, our RNA-sequencing analyses of FAM46C knockout testes revealed that mRNA levels of only nine genes were significantly altered compared to wild-type ones (q < 0.05). When considering alternate activities for FAM46C, in vitro assays demonstrated that FAM46C does not exhibit protein kinase or AMPylation activity against general substrates. Together, our data show that FAM46C in spermatids is a novel component in fastening the sperm head and flagellum.
      PubDate: Tue, 14 May 2019 00:00:00 GMT
      DOI: 10.1093/biolre/ioz083
      Issue No: Vol. 100, No. 6 (2019)
       
 
 
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