Oral Presentation ESA-SRB-ANZBMS 2021

Prenatal Androgen Excess Impairs Sexual Behavior in Adult Female Mice: Perspective on Sexual Dysfunction in PCOS (#73)

Nina Donaldson 1 , Mel Prescott 1 , Rebecca E Campbell 1 , Elodie Desroziers 1
  1. Center for Neuroendocrinology and Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand

Polycystic ovary syndrome (PCOS) is the most common infertility disorder worldwide, affecting 5-20% of reproductive aged women [1]. PCOS is characterised by high circulating androgen levels, oligo- or anovulation, and polycystic ovarian morphology [1]. PCOS patients also experience sexual dysfunction, such as decreased sexual desire, increased sexual dissatisfaction and gender dysphoria [2-4]. The origins of these sexual difficulties remain unidentified. The  well-characterized prenatally androgenized (PNA) mouse model of PCOS exhibit an adult hyperandrogenism, impaired sex steroid feedback and alterations in the neuronal network regulating reproductive function [5]. Thus, the PNA model of PCOS provides a powerful, pathology-based model to unravel a potential biological origins of sexual dysfunction in PCOS. We hypothesized that the PNA mouse model of PCOS will exhibit an impairment of female sexual behaviours. To model PCOS, female dams received injections of dihydrotestosterone (PNA) or oil vehicle (VEH) daily from gestational day 16 to 18. Adult female offspring were ovariectomized and implanted with a silastic capsule of estradiol to examine the female-typical sexual behaviour, lordosis; partner preference and male-like sexual behaviour. PNA females exhibited an overall reduction in lordosis behaviour compared to VEH females (p<0.01). Interestingly, partner preference and male-like sexual behaviour weren’t altered in PNA compare to VEH females. These results show for the first time that prenatal androgen exposure impairs sexual function. Neuronal activation after sexual behaviour is mainly not affected by prenatal androgen excess except in one part of the brain: the dorsomedial hypothalamus where a decrease in cFos immunoreactivity has been observed. Current experiments are underway to determine the neuronal target of prenatal androgen exposure implicated in the central control of lordosis. Taken together, this study open novel perspective on the origins of sexual dysfunction in women with PCOS and further investigation still remains to understand the biological mechanism of prenatal androgen exposure on the female brain and sexual function.

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