The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Characterization of Reproductive, Metabolic, and Endocrine Features of Polycystic Ovary Syndrome in Female Hyperandrogenic Mouse Models
Abstract
Polycystic ovary syndrome (PCOS) affects 5–10% of women of reproductive age, causing a range of reproductive, metabolic and endocrine defects including anovulation, infertility, hyperandrogenism, obesity, hyperinsulinism, and an increased risk of type 2 diabetes and cardiovascular disease. Hyperandrogenism is the most consistent feature of PCOS, but its etiology remains unknown, and ethical and logistic constraints limit definitive experimentation in humans to determine mechanisms involved. In this study, we provide the first comprehensive characterization of reproductive, endocrine, and metabolic PCOS traits in 4 distinct murine models of hyperandrogenism, comprising prenatal dihydrotestosterone (DHT, potent nonaromatizable androgen) treatment during days 16–18 of gestation, or long-term treatment (90 days from 21 days of age) with DHT, dehydroepiandrosterone (DHEA), or letrozole (aromatase inhibitor). Prenatal DHT-treated mature mice exhibited irregular estrous cycles, oligo-ovulation, reduced preantral follicle health, hepatic steatosis, and adipocyte hypertrophy, but lacked overall changes in body-fat composition. Long-term DHT treatment induced polycystic ovaries displaying unhealthy antral follicles (degenerate oocyte and/or > 10% pyknotic granulosa cells), as well as anovulation and acyclicity in mature (16-week-old) females. Long-term DHT also increased body and fat pad weights and induced adipocyte hypertrophy and hypercholesterolemia. Long-term letrozole-treated mice exhibited absent or irregular cycles, oligo-ovulation, polycystic ovaries containing hemorrhagic cysts atypical of PCOS, and displayed no metabolic features of PCOS. Long-term dehydroepiandrosterone treatment produced no PCOS features in mature mice. Our findings reveal that long-term DHT treatment replicated a breadth of ovarian, endocrine, and metabolic features of human PCOS and provides the best mouse model for experimental studies of PCOS pathogenesis.
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Cited by
Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome
Stener-Victorin, E., Padmanabhan, V., Walters, K. A., Campbell, R. E., Benrick, A., Giacobini, P., Dumesic, D. A., & Abbott, D. H. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa010 · Cited by 348
Self-citationNew Perspectives on the Pathogenesis of PCOS: Neuroendocrine Origins
Walters, K. A., Gilchrist, R. B., Ledger, W. L., Teede, H. J., Handelsman, D. J., & Campbell, R. E. (2018) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2018.08.005 · Cited by 186
Self-citationEstrogen as a key regulator of energy homeostasis and metabolic health
Mahboobifard, F., Pourgholami, M. H., Jorjani, M., Dargahi, L., Amiri, M., Sadeghi, S., & Tehrani, F. R. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113808 · Cited by 154
Androgens and ovarian function: translation from basic discovery research to clinical impact
Walters, K. A., Rodriguez Paris, V, Aflatounian, A., & Handelsman, D. J. (2019) · Journal of Endocrinology · doi:10.1530/joe-19-0096 · Cited by 104
Self-citationInositols in polycystic ovary syndrome: An overview on the advances
Facchinetti, F., Unfer, V., Dewailly, D., Kamenov, Z. A., Diamanti-Kandarakis, E., Laganà, A. S., Nestler, J. E., & Soulage, C. O. (2020) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2020.02.002 · Cited by 102
Metadata
- Authors
- Caldwell, A. S. L., Middleton, L. J., Jimenez, M., Desai, R., McMahon, A. C., Allan, C. M., Handelsman, D. J., & Walters, K. A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2014-08-01
- Volume
- 155
- Issue
- 8
- Pages
- 3146-3159
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2084300141
- Cited by
- 342
- References
- 62
- FWCI
- 16.42
- Type
- journal article
- Language
- en
- Open access
- closed
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- Caldwell, A. S. L., Middleton, L. J., Jimenez, M., Desai, R., McMahon, A. C., Allan, C. M., Handelsman, D. J., & Walters, K. A. (2014). Characterization of Reproductive, Metabolic, and Endocrine Features of Polycystic Ovary Syndrome in Female Hyperandrogenic Mouse Models. Endocrinology. https://doi.org/10.1210/en.2014-1196
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