Pathogenesis of Reproductive and Metabolic PCOS Traits in a Mouse Model.

Autor:	Rodriguez Paris V; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW 2052, Australia., Edwards MC; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW 2052, Australia.; Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, New South Wales 2139, Australia., Aflatounian A; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW 2052, Australia., Bertoldo MJ; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW 2052, Australia., Ledger WL; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW 2052, Australia., Handelsman DJ; Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, New South Wales 2139, Australia., Gilchrist RB; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW 2052, Australia., Walters KA; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW 2052, Australia.; Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, New South Wales 2139, Australia.
Jazyk:	angličtina
Zdroj:	Journal of the Endocrine Society [J Endocr Soc] 2021 Apr 07; Vol. 5 (6), pp. bvab060. Date of Electronic Publication: 2021 Apr 07 (Print Publication: 2021).
DOI:	10.1210/jendso/bvab060
Abstrakt:	Polycystic ovary syndrome (PCOS) is a common and heterogeneous disorder; however, the etiology and pathogenesis of PCOS are poorly understood and current management is symptom-based. Defining the pathogenesis of PCOS traits is important for developing early PCOS detection markers and new treatment strategies. Hyperandrogenism is a defining characteristic of PCOS, and studies support a role for androgen-driven actions in the development of PCOS. Therefore, we aimed to determine the temporal pattern of development of PCOS features in a well-characterized dihydrotestosterone (DHT)-induced PCOS mouse model after 2, 4, and 8 weeks of DHT exposure. Following 2 weeks of treatment, DHT induced the key PCOS reproductive features of acyclicity, anovulation, and multifollicular ovaries as well as a decrease in large antral follicle health. DHT-treated mice displayed the metabolic PCOS characteristics of increased body weight and exhibited increased visceral adiposity after 8 weeks of DHT treatment. DHT treatment also led to an increase in circulating cholesterol after 2 weeks of exposure and had an overall effect on fasting glucose levels, but not triglycerides, aspartate transaminase (AST) and alanine transaminase (ALT) levels, or hepatic steatosis. These data reveal that in this experimental PCOS mouse model, acyclicity, anovulation, and increased body weight are early features of a developing PCOS phenotype whereas adiposity, impaired glucose tolerance, dyslipidemia, and hepatic steatosis are later developing features of PCOS. These findings provide insights into the likely sequence of PCOS trait development and support the addition of body weight criteria to the early diagnosis of PCOS. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
Databáze:	MEDLINE
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