Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models
Abstract
BACKGROUND: Androgens and the androgen receptor (AR) have well known roles in male reproduction, and recent genetic mouse models inactivating the Ar gene have conclusively defined a role for androgens in female reproduction. In males, AR gene inactivation severely disrupts spermatogenesis by interrupting completion of meiosis, thereby eliminating production of mature sperm leading to male sterility. These effects have overshadowed the study of additional post-meiotic androgen effects required for the production of fully functional spermatozoa, as well as the production of females with complete androgen insensitivity which cannot be produced by natural breeding. However, these limitations have been overcome by the creation of global and cell-specific AR knockout (ARKO) mouse models using Cre-LoxP genetic engineering. METHODS: Pubmed searches were carried out using the following search terms: androgen receptor, knockout mouse and fertility. Articles published before the end of November 2009 were included. RESULTS: These experimental models have identified cell-specific AR-mediated androgen actions in testis and androgen actions in sex accessory glands independent of testicular effects which are crucial for sperm maturation, motion and fertilizing ability. The ability to produce homozygous ARKO females has revealed that AR-mediated androgen actions are important for normal female fertility. AR function is required for full functionality in follicle health, development and ovulation through both intra-ovarian and neuroendocrine mechanisms. CONCLUSIONS: ARKO mouse models provide valuable tools to unravel novel roles of AR-mediated actions in male and female reproductive function, and new insights into the role of androgens in human reproductive function.
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The Tfm mouse model has limitations, including potential residual AR activity due to the production of a truncated AR protein.
“the Tfm mouse model has a number of limitations, including potential residual AR activity due to the production of a truncated AR protein.”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [133]
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Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance
Handelsman, D. J., Hirschberg, A. L., & Bermon, S. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00020 · Cited by 594 · see citing works
Self-citationMinireview: the androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene?
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- Authors
- Walters, K. A., Simanainen, U., & Handelsman, D. J.
- Affiliations
- The University of Sydney (AU)
- Venue
- Human Reproduction Update
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-03-15
- Volume
- 16
- Issue
- 5
- Pages
- 543-558
- ISSN
- 1355-4786 (ISSN-L)
- 1460-2369
- OpenAlex
- W2127056379
- Cited by
- 183
- References
- 166
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 11 · 2023: 4 · 2022: 22 · 2021: 12 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 13 · 2015: 13 · 2014: 21 · 2013: 14 · 2012: 13
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction Update (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Institute NSW
- University of Sydney
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Reproductive biology and impacts on aquatic species
- Keywords
- androgen receptor, androgen receptor knockout mice, androgen action, male fertility, female fertility, spermatogenesis, sperm maturation, complete androgen insensitivity syndrome, accessory sex glands, ovulation, folliculogenesis, neuroendocrine regulation
- MeSH terms
- Animals, Female, Fertility, Genetic Engineering, Ovarian Follicle, Humans, Male, Receptors, Androgen, Sertoli Cells, Mice, Knockout, Models, Animal, Mice
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