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Publisher: Oxford University Press   (Total: 396 journals)

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Showing 1 - 200 of 396 Journals sorted alphabetically
ACS Symposium Series     Full-text available via subscription   (SJR: 0.189, CiteScore: 0)
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Adaptation     Hybrid Journal   (Followers: 8, SJR: 0.143, CiteScore: 0)
Advances in Nutrition     Hybrid Journal   (Followers: 44, SJR: 2.196, CiteScore: 5)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.434, CiteScore: 1)
African Affairs     Hybrid Journal   (Followers: 63, SJR: 1.869, CiteScore: 2)
Age and Ageing     Hybrid Journal   (Followers: 91, 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: 7)
American Historical Review     Hybrid Journal   (Followers: 148, SJR: 0.467, CiteScore: 1)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 40, SJR: 2.113, CiteScore: 3)
American J. of Clinical Nutrition     Hybrid Journal   (Followers: 144, SJR: 3.438, CiteScore: 6)
American J. of Epidemiology     Hybrid Journal   (Followers: 172, SJR: 2.713, CiteScore: 3)
American J. of Hypertension     Hybrid Journal   (Followers: 25, SJR: 1.322, CiteScore: 3)
American J. of Jurisprudence     Hybrid Journal   (Followers: 18, SJR: 0.281, CiteScore: 1)
American J. of Legal History     Full-text available via subscription   (Followers: 8, SJR: 0.116, CiteScore: 0)
American Law and Economics Review     Hybrid Journal   (Followers: 27, SJR: 1.053, CiteScore: 1)
American Literary History     Hybrid Journal   (Followers: 15, SJR: 0.391, CiteScore: 0)
Analysis     Hybrid Journal   (Followers: 21, SJR: 1.038, CiteScore: 1)
Animal Frontiers     Hybrid Journal  
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 14, SJR: 1.423, CiteScore: 3)
Annals of Botany     Hybrid Journal   (Followers: 35, SJR: 1.721, CiteScore: 4)
Annals of Oncology     Hybrid Journal   (Followers: 42, SJR: 5.599, CiteScore: 9)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 10, SJR: 0.722, CiteScore: 1)
Annals of Work Exposures and Health     Hybrid Journal   (Followers: 33, SJR: 0.728, CiteScore: 2)
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: 56, 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: 20)
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: 42, SJR: 0.146, CiteScore: 0)
Behavioral Ecology     Hybrid Journal   (Followers: 52, SJR: 1.871, CiteScore: 3)
Bioinformatics     Hybrid Journal   (Followers: 301, 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: 1, SJR: 0.146, CiteScore: 0)
Biostatistics     Hybrid Journal   (Followers: 17, SJR: 1.553, CiteScore: 2)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 164, SJR: 2.115, CiteScore: 3)
BJA Education     Hybrid Journal   (Followers: 64)
Brain     Hybrid Journal   (Followers: 68, SJR: 5.858, CiteScore: 7)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 47, 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: 35, SJR: 2.161, CiteScore: 2)
British J. of Aesthetics     Hybrid Journal   (Followers: 26, SJR: 0.508, CiteScore: 1)
British J. of Criminology     Hybrid Journal   (Followers: 575, SJR: 1.828, CiteScore: 3)
British J. of Social Work     Hybrid Journal   (Followers: 88, SJR: 1.019, CiteScore: 2)
British Medical Bulletin     Hybrid Journal   (Followers: 7, SJR: 1.355, CiteScore: 3)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 32)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 4, SJR: 1.376, CiteScore: 1)
Cambridge J. of Economics     Hybrid Journal   (Followers: 61, SJR: 0.764, CiteScore: 2)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 11, SJR: 2.438, CiteScore: 4)
Cambridge Quarterly     Hybrid Journal   (Followers: 9, 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: 45, SJR: 3.892, CiteScore: 6)
CESifo Economic Studies     Hybrid Journal   (Followers: 17, SJR: 0.483, CiteScore: 1)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.42, CiteScore: 3)
Children and Schools     Hybrid Journal   (Followers: 5, SJR: 0.246, CiteScore: 0)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 4, 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: 9, 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: 25, SJR: 0.123, CiteScore: 0)
Clean Energy     Open Access   (Followers: 1)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 65, SJR: 5.051, CiteScore: 5)
Clinical Kidney J.     Open Access   (Followers: 3, SJR: 1.163, CiteScore: 2)
Communication Theory     Hybrid Journal   (Followers: 21, SJR: 2.424, CiteScore: 3)
Communication, Culture & Critique     Hybrid Journal   (Followers: 26, 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: 2, 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: 5, SJR: 0.906, CiteScore: 1)
Critical Values     Full-text available via subscription  
Current Developments in Nutrition     Open Access  
Current Legal Problems     Hybrid Journal   (Followers: 27)
Current Zoology     Full-text available via subscription   (Followers: 2, SJR: 1.164, CiteScore: 2)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 8, SJR: 1.791, CiteScore: 3)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 13, 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: 3)
Early Music     Hybrid Journal   (Followers: 15, SJR: 0.139, CiteScore: 0)
Economic Policy     Hybrid Journal   (Followers: 39, SJR: 3.584, CiteScore: 3)
ELT J.     Hybrid Journal   (Followers: 24, SJR: 0.942, CiteScore: 1)
English Historical Review     Hybrid Journal   (Followers: 51, SJR: 0.612, CiteScore: 1)
English: J. of the English Association     Hybrid Journal   (Followers: 14, SJR: 0.1, CiteScore: 0)
Environmental Entomology     Full-text available via subscription   (Followers: 11, SJR: 0.818, CiteScore: 2)
Environmental Epigenetics     Open Access   (Followers: 3)
Environmental History     Hybrid Journal   (Followers: 27, SJR: 0.408, CiteScore: 1)
EP-Europace     Hybrid Journal   (Followers: 2, 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: 16, SJR: 0.113, CiteScore: 0)
European Heart J.     Hybrid Journal   (Followers: 57, SJR: 9.315, CiteScore: 9)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 9, SJR: 3.625, CiteScore: 3)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 1)
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: 181, SJR: 0.694, CiteScore: 1)
European J. of Orthodontics     Hybrid Journal   (Followers: 4, SJR: 1.279, CiteScore: 2)
European J. of Public Health     Hybrid Journal   (Followers: 20, 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: 29, SJR: 0.702, CiteScore: 1)
European Sociological Review     Hybrid Journal   (Followers: 40, SJR: 2.728, CiteScore: 3)
Evolution, Medicine, and Public Health     Open Access   (Followers: 11)
Family Practice     Hybrid Journal   (Followers: 15, SJR: 1.018, CiteScore: 2)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 12, SJR: 1.492, CiteScore: 4)
Fems Microbiology Letters     Hybrid Journal   (Followers: 24, SJR: 0.79, CiteScore: 2)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 30, 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: 23, SJR: 1.425, CiteScore: 1)
Forest Science     Hybrid Journal   (Followers: 7, 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: 32, SJR: 0.118, CiteScore: 0)
French Studies     Hybrid Journal   (Followers: 20, SJR: 0.148, CiteScore: 0)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.152, CiteScore: 0)
Gastroenterology Report     Open Access   (Followers: 2)
Genome Biology and Evolution     Open Access   (Followers: 12, SJR: 2.578, CiteScore: 4)
Geophysical J. Intl.     Hybrid Journal   (Followers: 35, SJR: 1.506, CiteScore: 3)
German History     Hybrid Journal   (Followers: 22, SJR: 0.161, CiteScore: 0)
GigaScience     Open Access   (Followers: 3, SJR: 5.022, CiteScore: 7)
Global Summitry     Hybrid Journal   (Followers: 1)
Glycobiology     Hybrid Journal   (Followers: 14, SJR: 1.493, CiteScore: 3)
Health and Social Work     Hybrid Journal   (Followers: 56, SJR: 0.388, CiteScore: 1)
Health Education Research     Hybrid Journal   (Followers: 15, SJR: 0.854, CiteScore: 2)
Health Policy and Planning     Hybrid Journal   (Followers: 23, SJR: 1.512, CiteScore: 2)
Health Promotion Intl.     Hybrid Journal   (Followers: 22, SJR: 0.812, CiteScore: 2)
History Workshop J.     Hybrid Journal   (Followers: 29, SJR: 1.278, CiteScore: 1)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 28, SJR: 0.105, CiteScore: 0)
Human Communication Research     Hybrid Journal   (Followers: 13, SJR: 2.146, CiteScore: 3)
Human Molecular Genetics     Hybrid Journal   (Followers: 8, SJR: 3.555, CiteScore: 5)
Human Reproduction     Hybrid Journal   (Followers: 71, SJR: 2.643, CiteScore: 5)
Human Reproduction Open     Open Access  
Human Reproduction Update     Hybrid Journal   (Followers: 19, SJR: 5.317, CiteScore: 10)
Human Rights Law Review     Hybrid Journal   (Followers: 56, SJR: 0.756, CiteScore: 1)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 51, SJR: 1.591, CiteScore: 3)
ICSID Review     Hybrid Journal   (Followers: 10)
ILAR J.     Hybrid Journal   (Followers: 2, 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: 35, SJR: 0.249, CiteScore: 1)
Inflammatory Bowel Diseases     Hybrid Journal   (Followers: 43, SJR: 2.511, CiteScore: 4)
Information and Inference     Free  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 8, SJR: 1.319, CiteScore: 2)
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: 58, SJR: 1.505, CiteScore: 3)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 24)
Intl. Health     Hybrid Journal   (Followers: 5, 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: 62, SJR: 0.601, CiteScore: 1)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 218, 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: 25, SJR: 0.223, CiteScore: 1)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 9, 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: 9, SJR: 1.545, CiteScore: 1)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 35, 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: 35, SJR: 1.465, CiteScore: 3)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 23, SJR: 0.401, CiteScore: 1)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 9, SJR: 0.983, CiteScore: 1)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 44, SJR: 2.581, CiteScore: 2)
Intl. Studies Review     Hybrid Journal   (Followers: 22, SJR: 1.201, CiteScore: 1)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 1, SJR: 0.15, CiteScore: 0)
ITNOW     Hybrid Journal   (Followers: 1, SJR: 0.103, CiteScore: 0)
J. of African Economies     Hybrid Journal   (Followers: 15, 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: 4, SJR: 0.585, CiteScore: 1)
J. of Biochemistry     Hybrid Journal   (Followers: 42, SJR: 1.226, CiteScore: 2)
J. of Burn Care & Research     Hybrid Journal   (Followers: 9, SJR: 0.768, CiteScore: 2)
J. of Chromatographic Science     Hybrid Journal   (Followers: 18, SJR: 0.36, CiteScore: 1)
J. of Church and State     Hybrid Journal   (Followers: 11, SJR: 0.139, CiteScore: 0)
J. of Communication     Hybrid Journal   (Followers: 51, SJR: 4.411, CiteScore: 5)
J. of Competition Law and Economics     Hybrid Journal   (Followers: 35, SJR: 0.33, CiteScore: 0)
J. of Complex Networks     Hybrid Journal   (Followers: 2, SJR: 1.05, CiteScore: 4)
J. of Computer-Mediated Communication     Open Access   (Followers: 26, SJR: 2.961, CiteScore: 6)
J. of Conflict and Security Law     Hybrid Journal   (Followers: 12, SJR: 0.402, CiteScore: 0)
J. of Consumer Research     Full-text available via subscription   (Followers: 42, SJR: 5.856, CiteScore: 5)

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Journal Cover
Human Reproduction Update
Journal Prestige (SJR): 5.317
Citation Impact (citeScore): 10
Number of Followers: 19  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1355-4786 - ISSN (Online) 1460-2369
Published by Oxford University Press Homepage  [396 journals]
  • A systematic review and meta-analysis reveals pervasive effects of
           germline mitochondrial replacement on components of health
    • Authors: Dobler R; Dowling D, Morrow E, et al.
      Pages: 519 - 534
      Abstract: BACKGROUNDMitochondrial replacement, a form of nuclear transfer, has been proposed as a germline therapy to prevent the transmission of mitochondrial diseases. Mitochondrial replacement therapy has been licensed for clinical application in the UK, and already carried out in other countries, but little is known about negative or unintended effects on the health of offspring born using this technique.OBJECTIVE AND RATIONALEStudies in invertebrate models have used techniques that achieve mitochondrial replacement to create offspring with novel combinations of mitochondrial and nuclear genotype. These have demonstrated that the creation of novel mitochondrial–nuclear interactions can lead to alterations in offspring characteristics, such as development rates, fertility and longevity. However, it is currently unclear whether such interactions could similarly affect the outcomes of vertebrate biomedical studies, which have sought to assess the efficacy of the replacement therapy.SEARCH METHODSThis systematic review addresses whether the effects of mitochondrial replacement on offspring characteristics differ in magnitude between biological (conducted on invertebrate models, with an ecological or evolutionary focus) and biomedical studies (conducted on vertebrate models, with a clinical focus). Studies were selected based on a key-word search in ‘Web of Science’, complemented by backward searches of reviews on the topic of mitochondrial–nuclear (mito-nuclear) interactions. In total, 43 of the resulting 116 publications identified in the search contained reliable data to estimate effect sizes of mitochondrial replacement. We found no evidence of publication bias when examining effect-size estimates across sample sizes.OUTCOMESMitochondrial replacement consistently altered the phenotype, with significant effects at several levels of organismal performance and health, including gene expression, anatomy, metabolism and life-history. Biomedical and biological studies, while differing in the methods used to achieve mitochondrial replacement, showed only marginally significant differences in effect-size estimates (−0.233 [CI: −0.495 to −0.011]), with larger effect-size estimates in biomedical studies (0.697 [CI: 0.450–0.956]) than biological studies (0.462 [CI: 0.287–0.688]). Humans showed stronger effects than other species. Effects of mitochondrial replacement were also stronger in species with a higher basal metabolic rate. Based on our results, we conducted the first formal risk analysis of mitochondrial replacement, and conservatively estimate negative effects in at least one in every 130 resulting offspring born to the therapy.WIDER IMPLICATIONSOur findings suggest that mitochondrial replacement may routinely affect offspring characteristics across a wide array of animal species, and that such effects are likely to extend to humans. Studies in invertebrate models have confirmed mito-nuclear interactions as the underpinning cause of organismal effects following mitochondrial replacement. This therefore suggests that mito-nuclear interactions are also likely to be contributing to effects seen in biomedical studies, on vertebrate models, whose effect sizes exceeded those of biological studies. Our results advocate the use of safeguards that could offset any negative effects (defining any unintended effect as being negative) mediated by mito-nuclear interactions following mitochondrial replacement in humans, such as mitochondrial genetic matching between donor and recipient. Our results also suggest that further research into the molecular nature of mito-nuclear interactions would be beneficial in refining the clinical application of mitochondrial replacement, and in establishing what degree of variation between donor and patient mitochondrial DNA haplotypes is acceptable to ensure ‘haplotype matching’.
      PubDate: Fri, 11 May 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy018
      Issue No: Vol. 24, No. 5 (2018)
  • The contribution of human sperm proteins to the development and epigenome
           of the preimplantation embryo
    • Authors: Castillo J; Jodar M, Oliva R.
      Pages: 535 - 555
      Abstract: BACKGROUNDKnowledge of the proteomic composition of the gametes is essential to understand reproductive functions. Most of the sperm proteins are related to spermatogenesis and sperm function, but less abundant protein groups with potential post-fertilization roles have also been detected. The current data are challenging our understanding of sperm biology and functionality, demanding an integrated analysis of the proteomic and RNA-seq datasets available for spermatozoa, oocytes and early embryos, in order to unravel the impact of the male gamete on the generation of the new individual.OBJECTIVE AND RATIONALEThe aim of this review is to compile human sperm proteins and to identify and infer their origin and discuss their relevance during oocyte fecundation, preimplantation embryogenesis and epigenetic inheritance.SEARCH METHODSThe scientific literature was comprehensively searched for proteomic studies on human sperm, oocytes, embryos, and additional reproductive cells and fluids. Proteins were compiled and functionally classified according to Gene Ontology annotations and the mouse phenotypes integrated into the Mouse Genome Informatics database. High-throughput RNA datasets were used to decipher the origin of embryo proteins. The tissue origin of sperm proteins was inferred on the basis of RNA-seq and protein data available in the Human Protein Atlas database.OUTCOMESSo far, 6871 proteins have been identified and reported in sperm, 1376 in the oocyte and 1300 in blastocyst. With a deeper analysis of the sperm proteome, 103 proteins with known roles in the processes of fertilization and 93 with roles in early embryo development have been identified. Additionally, 560 sperm proteins have been found to be involved in modulating gene expression by regulation of transcription, DNA methylation, histone post-translational modifications and non-coding RNA biogenesis. Some of these proteins may be critical for gene expression regulation after embryo genome activation, and therefore, may be potentially involved in epigenetic transmission of altered phenotypes. Furthermore, the integrative analysis of the sperm, oocyte and blastocyst proteomes and transcriptomes revealed a set of embryo proteins with an exclusive paternal origin, some of which are crucial for correct embryogenesis and, possibly, for modulation of the offspring phenotype. The analysis of the expression of sperm proteins, at both RNA and protein levels, in tissues not only from the male reproductive tract but also from peripheral organs, has suggested a putative extra-testicular origin for some sperm proteins. These proteins could be imported into sperm from the accessory sex glands and other tissues, most likely through exosomes.WIDER IMPLICATIONSThese integrative proteome and transcriptome analyses focused on specific groups of proteins, rather than on enriched pathways, identified important sperm proteins which may be involved in early embryogenesis and provided evidence which could support the hypothesis of paternal epigenetic inheritance. The putative extra-testicular origin of some sperm proteins suggests not only the involvement of accessory sex glands in fertilization and epigenetic information transmission, but also that some proteins from additional organs could possibly contribute information to the offspring phenotype. These findings should stimulate further research in the field.
      PubDate: Wed, 23 May 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy017
      Issue No: Vol. 24, No. 5 (2018)
  • Epigenetic regulation in development: is the mouse a good model for the
    • Authors: Hanna C; Demond H, Kelsey G.
      Pages: 556 - 576
      Abstract: BACKGROUNDOver the past few years, advances in molecular technologies have allowed unprecedented mapping of epigenetic modifications in gametes and during early embryonic development. This work is allowing a detailed genomic analysis, which for the first time can answer long-standing questions about epigenetic regulation and reprogramming, and highlights differences between mouse and human, the implications of which are only beginning to be explored.OBJECTIVE AND RATIONALEIn this review, we summarise new low-cell molecular methods enabling the interrogation of epigenetic information in gametes and early embryos, the mechanistic insights these have provided, and contrast the findings in mouse and human.SEARCH METHODSRelevant studies were identified by PubMed search.OUTCOMESWe discuss the levels of epigenetic regulation, from DNA modifications to chromatin organisation, during mouse gametogenesis, fertilisation and pre- and post-implantation development. The recently characterised features of the oocyte epigenome highlight its exceptionally unique regulatory landscape. The chromatin organisation and epigenetic landscape of both gametic genomes are rapidly reprogrammed after fertilisation. This extensive epigenetic remodelling is necessary for zygotic genome activation, but the mechanistic link remains unclear. While the vast majority of epigenetic information from the gametes is erased in pre-implantation development, new insights suggest that repressive histone modifications from the oocyte may mediate a novel mechanism of imprinting. To date, the characterisation of epigenetics in human development has been almost exclusively limited to DNA methylation profiling; these data reinforce that the global dynamics are conserved between mouse and human. However, as we look closer, it is becoming apparent that the mechanisms regulating these dynamics are distinct. These early findings emphasise the importance of investigations of fundamental epigenetic mechanisms in both mouse and humans.WIDER IMPLICATIONSFailures in epigenetic regulation have been implicated in human disease and infertility. With increasing maternal age and use of reproductive technologies in countries all over the world, it is becoming ever more important to understand the necessary processes required to establish a developmentally competent embryo. Furthermore, it is essential to evaluate the extent to which these epigenetic patterns are sensitive to such technologies and other adverse environmental exposures.
      PubDate: Tue, 10 Jul 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy021
      Issue No: Vol. 24, No. 5 (2018)
  • Is it time for a paradigm shift in drug research and development in
    • Authors: Guo S; Groothuis P.
      Pages: 577 - 598
      Abstract: BACKGROUNDThe drug research and development (R&D) for endometriosis/adenomyosis has been painfully slow. Most completed clinical trials on endometriosis did not publish their results, and presumably failed. While few published trials did report how they foundered, the reasons why they failed are often completely unclear. Surprisingly, there has been no open discussion on why these trials failed. If the causes for these failed trials remain unelucidated, mistakes made in these failed trials may be repeated in the future. Since failure can be infinitely more instructive and educational than success, elucidating the causes for failed clinical trials may yield a treasure trove for future drug R&D. Given our growing understanding of the natural history of ectopic endometrium, it is also important to make an inventory of biologicals/compounds that are currently under development to see where we stand and whether they would stand a better chance of gaining regulatory approval than their predecessors.OBJECTIVE AND RATIONALEWe provide an overview of all compounds under clinical investigation and in development in order to assess the evolution of R&D since the last inventory, reported in 2013. We also have attempted to analyse selected failed clinical trials in the context of published translational/preclinical research and our growing understanding of the natural history of endometriotic/adenomyotic lesions, in the hope that the lessons learned will steer investigators toward the right track in future drug R&D.SEARCH METHODSWe searched and a database containing information on drugs gathered daily by Thomson Reuters from a wide range of sources (e.g. patent offices, biomedical literature, congresses, symposia, meetings, company information, regulatory information) for all therapeutic compounds that have undergone or are under clinical trials, or in the developmental stage, and then searched PubMed and Google to determine their publication status using trial identifiers. For trials that were completed at least 2 years ago and have, or have not, published their results, a PubMed search was performed using the name of the therapeutic that has been tested and ‘endometriosis’ or ‘adenomyosis’ to identify published preclinical studies prior to the launch of the trial. For those published trials, the cited preclinical studies were also retrieved and scrutinized.OUTCOMESDespite repeated calls for more transparency, only a small fraction of completed trials on endometriosis has been published. A large number of ‘novel’ compounds under development are simply repurposed drugs, which seem to be ill-prepared to combat the fibroproliferative nature of endometriosis/adenomyosis. This sobering picture indicates an alarming innovation ‘drought’ in the drug R&D front, resulting in trickling drug pipelines.Some trials foundered owing to unanticipated serious side-effects, or because attempts were made to suppress a target that can be compensated for by redundant pathways, but many failed in efficacy, indicating that the translational value of the current models is seriously questionable. All existing animal models of endometriosis do not recapitulate the key features of human conditions.WIDER IMPLICATIONSThe glaring innovation drought in drug R&D for endometriosis/adenomyosis should sound alarms to all stake-holders. The failed clinical trials in endometriosis also indicate that some past research had serious deficiencies. In light of the recent understanding of the natural history of ectopic endometrium, it is perhaps time to shift the research paradigm and revamp our research focus and priorities.
      PubDate: Mon, 11 Jun 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy020
      Issue No: Vol. 24, No. 5 (2018)
  • Clinical relevance of genetic variants of gonadotrophins and their
           receptors in controlled ovarian stimulation: a systematic review and
    • Authors: Alviggi C; Conforti A, Santi D, et al.
      Pages: 599 - 614
      Abstract: BACKGROUNDGenotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach to controlled ovarian stimulation (COS). However, the validity of such an approach remains to be established.OBJECTIVE AND RATIONALETo define the impact of specific genotype profiles of follicle-stimulating hormone, luteinizing hormone and their receptors (FSHR, LHR and LHCGR) on ovarian stimulation outcome. Specifically, our aim was to identify polymorphisms that could be useful in clinical practice, and those that need further clinical investigation.SEARCH METHODSA systematic review followed by a meta-analysis was performed according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines without time restriction. We searched the PubMed/MEDLINE, Cochrane Library, SCOPUS and EMBASE databases to identify all relevant studies published before January 2017. Only clinical trials published as full-text articles in peer-reviewed journals were included. The primary outcome was the number of oocytes retrieved.OUTCOMESFifty-seven studies were assessed for eligibility, 33 of which were included in the qualitative and quantitative analyses. Data were independently extracted using quality indicators. COS outcomes related to seven polymorphisms (FSHR [rs6165], FSHR [rs6166], FSHR [rs1394205], LHB [rs1800447], LHB [rs1056917], LHCGR [rs2293275] and LHCGR [rs13405728]) were evaluated. More oocytes were retrieved from FSHR (rs6165) AA homozygotes (five studies, 677 patients, weighted mean difference [WMD]: 1.85, 95% CI: 0.85–2.85, P < 0.001; I2 = 0%) than from GG homozygotes and AG heterozygotes (four studies, 630 patients, WMD: 1.62, 95% CI: 0.28–2.95, P = 0.020; I2 = 56%). Moreover, stimulation duration was shorter in FSHR (rs6165) AA homozygotes than in AG carriers (three studies, 588 patients, WMD −0.48, 95% CI: −0.87 to −0.10, P = 0.010, I2 = 44%). A higher number of oocytes (21 studies, 2632 patients WMD: 0.84, 95% CI: 0.19 to 1.49, P = 0.01, I2 = 76%) and metaphase II oocytes (five studies, 608 patients, WMD: 1.03, 95% CI: 0.01–2.05, P = 0.050, I2 = 0%) was observed in AA than in GG homozygote carriers. FSH consumption was significantly lower in FSHR (rs1394205) GG homozygotes (three studies, 411 patients, WMD: −1294.61 IU, 95% CI: −593.08 to −1996.14 IU, P = 0.0003, I2 = 99%) and AG heterozygotes (three studies, 367 patients, WMD: −1014.36 IU, 95% CI: −364.11 to −1664.61 IU, P = 0.002, I2 = 99%) than in AA homozygotes.WIDER IMPLICATIONSThese results support the clinical relevance of specific genotype profiles on reproductive outcome. Further studies are required to determine their application in a pharmacogenomic approach to ovarian stimulation.
      PubDate: Mon, 18 Jun 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy019
      Issue No: Vol. 24, No. 5 (2018)
  • Ethics of oocyte banking for third-party assisted reproduction: a
           systematic review
    • Authors: Kool E; Bos A, van der Graaf R, et al.
      Pages: 615 - 635
      Abstract: BACKGROUNDThe demand for donor oocytes has increased dramatically over the years. Today people in need of ART with the use of donor oocytes can appeal to commercial or public donor oocyte banks. The introduction of oocyte banks has shed a new light on the practice of ART using donor oocytes. The establishment and maintenance of oocyte banks should be sensitive to the ethical considerations. However, it is currently unclear which ethical aspects have to be taken into account.OBJECTIVE AND RATIONALEThe aim of this article is to identify the ethical aspects of establishing and maintaining oocyte banks for third-party ART.SEARCH METHODSA systematic search was performed in July 2016 and February 2017 in both PubMed and Embase using a search string that combined synonyms for oocytes, donation or banking, reproductive care and ethics. We included a wide variety of English-language articles with a reasoned description of ethical aspects or moral considerations on oocyte donation or banking for third-party ART.OUTCOMESThe practice of oocyte banking consists of three components, namely, the intake, storage and distribution of donor oocytes, and each is associated with multiple ethical challenges. The majority of the literature discusses ethical aspects with regard to the intake of donor oocytes, taking into account both the interests of the donor and those of the potential child. Ethical aspects related to the donor are the risks and psychosocial impact of donation, motivations and compensation in donor recruitment, and requirements for informed consent. Ethical aspects related to the potential child are 2-fold: first, the welfare standard and the selection of donors, and second, anonymity and disclosure. Ethical aspects of storing donor oocytes for ART are quality standards, confidentiality, issues of ownership and control, and international transport of donor oocytes. Ethical aspects of the distribution of donor oocytes concern the selection of recipients and the acceptability of treatment of ‘non-traditional’ families in particular, prioritization of recipients in case of scarcity, cross-border reproductive care, matching of recipients and donor oocytes, informed consent and counselling for recipients.WIDER IMPLICATIONSOur review demonstrates that multiple ethical aspects have to be taken into account when establishing and maintaining an oocyte bank. Yet, for many of these aspects there is no consensus regarding what approach should be employed. Remarkably, the existing literature focuses mainly on ethical aspects related to the intake of donor oocytes, while aspects related to storage and distribution of donor oocytes are less often addressed. An important gap in the existing literature should therefore be acknowledged. To conclude, our findings can serve as a starting point for clinicians in the field of ART, to conceptualize what challenges arise when establishing and maintaining oocyte banks for third-party ART. The review may also stimulate policy makers to set up a trustworthy and adaptive governance structure for the intake, storage and distribution of donor oocytes.
      PubDate: Mon, 14 May 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy016
      Issue No: Vol. 24, No. 5 (2018)
  • Vascularization in endometriosis and its clinical applications
    • Authors: Galazis N; Raza A.
      Pages: 636 - 637
      PubDate: Fri, 20 Jul 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy023
      Issue No: Vol. 24, No. 5 (2018)
  • Reply: Vascularization in endometriosis and its clinical applications
    • Authors: Laschke M; Menger M.
      Pages: 638 - 638
      PubDate: Fri, 20 Jul 2018 00:00:00 GMT
      DOI: 10.1093/humupd/dmy024
      Issue No: Vol. 24, No. 5 (2018)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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