Short‐term rapamycin administration elevated testosterone levels and exacerbated reproductive disorder in dehydroepiandrosterone‐induced polycystic ovary syndrome mice

Abstract

Background Polycystic ovary syndrome (PCOS) is a multifactorial endocrinopathy that affects reproduction and metabolism. Mammalian target of rapamycin (mTOR) has been shown to participate in female reproduction under physiological and pathological conditions. This study aimed to investigate the role of mTOR complex 1 (mTORC1) signaling in dehydroepiandrosterone (DHEA)-induced PCOS mice. Results Female C57BL/6J mice were randomly assigned into three groups: control group, DHEA group, and DHEA + rapamycin group. All DHEA-treated mice were administered 6 mg/100 g DHEA for 21 consecutive days, and the DHEA + rapamycin group was intraperitoneally injected with 4 mg/kg rapamycin every other day for the last 14 days of the DHEA treatment. There was no obvious change in the expression of mTORC1 signaling in the ovaries of the control and DHEA groups. Rapamycin did not protect against DHEA-induced acyclicity and PCO morphology, but impeded follicle development and elevated serum testosterone levels in DHEA-induced mice, which was related with suppressed Hsd3b1, Cyp17a1, and Cyp19a1 expression. Moreover, rapamycin also exacerbated insulin resistance but relieved lipid metabolic disturbance in the short term. Conclusions Rapamycin exacerbated reproductive imbalance in DHEA-induced PCOS mice, which characterized by elevated testosterone levels and suppressed steroid synthesis. This underscores the need for new mTORC1-specific and tissue-specific mTOR-related drugs for reproductive disorders.

Down‐regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome

“…To determine the role of lysine crotonylation in PCOS development, dehydroepiandrosterone (DHEA)‐induced PCOS mice were modeled according to a previous study 21 . Body weight (BW), estrous cycle, sex hormone levels, and ovarian tissue morphology were monitored.…”

“…To determine the role of lysine crotonylation in PCOS development, dehydroepiandrosterone (DHEA)‐induced PCOS mice were modeled according to a previous study. 21 Body weight (BW), estrous cycle, sex hormone levels, and ovarian tissue morphology were monitored. Both control and DHEA‐modeled mice were well developed before the experimental intervention, and there were no significant differences in their behavior and physical signs.…”

ENPP1 is correlated with insulin resistance and lipid metabolism disorders in the rat model of polycystic ovary syndrome

“…In addition, excess androgens can also lead to visceral obesity, i.e., hypertrophy of visceral and subcutaneous fat cells, as veri ed in this study, as well as dyslipidaemia. It is believed that androgen excess leads to PCOS exhibiting IR and visceral obesity and further promotes androgen secretion from the ovaries and adrenal glands, thus fostering a vicious cycle of PCOS [26] .…”