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Biological Sciences

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Several mouse models have been developed to study polycystic ovarian syndrome (PCOS), a leading cause of infertility in women. Treatment of mice with dihydrotestosterone (DHT) for 90-days causes ovarian and metabolic phenotypes similar to women with PCOS. We used this 90-day DHT treatment paradigm to investigate the variable incidence and heterogeneity in two inbred mouse strains, NOD/ShiLtJ and 129S1/SvlmJ. NOD mice naturally develop type 1 diabetes, and recent meta-analysis found increased androgen excess and PCOS in women with type 1 diabetes. 129S1 mice are commonly used in genetic manipulations. Both NOD and 129S1 DHT treated mice had early vaginal opening, increased anogenital distance and altered estrus cycles compared to control animals. Additionally, both NOD and 129S1 mice had reduced numbers of corpora lutea after DHT exposure, while NOD mice had decreased numbers of preantral follicles and 129S1 mice had reduced numbers of small antral follicles. NOD mice had increased body weight, decreased white adipocyte size, and improved glucose sensitivity in response to DHT, while 129S1 mice had increased body weight and white adipocyte size. NOD mice had increased expression of Adiponectin, Cidea, Srebp1a and Srebp1b and 129S1 mice had decreased Pparg in the white adipose tissues, while both NOD and 129S1 mice had increased expression of Glut4 and Prdm16 suggesting DHT may differentially affect glucose transport, thermogenesis, and lipid storage in white adipose tissue. DHT causes different ovarian and metabolic responses in NOD and 129S1 mice suggesting that strain differences may allow further elucidation of genetic contributions to PCOS.


This article was originally published in Endocrinology. The full-text article from the publisher can be found here.