Centre for Neuroendocrinology and Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Front Endocrinol (Lausanne). 2023 Feb 15;14:1116482. doi: 10.3389/fendo.2023.1116482. eCollection 2023.
Polycystic ovary syndrome (PCOS) is the most common infertility disorder worldwide, typically characterised by high circulating androgen levels, oligo- or anovulation, and polycystic ovarian morphology. Sexual dysfunction, including decreased sexual desire and increased sexual dissatisfaction, is also reported by women with PCOS. The origins of these sexual difficulties remain largely unidentified. To investigate potential biological origins of sexual dysfunction in PCOS patients, we asked whether the well-characterized, prenatally androgenized (PNA) mouse model of PCOS exhibits modified sex behaviours and whether central brain circuits associated with female sex behaviour are differentially regulated. As a male equivalent of PCOS is reported in the brothers of women with PCOS, we also investigated the impact of maternal androgen excess on the sex behaviour of male siblings.
Adult male and female offspring of dams exposed to dihydrotestosterone (PNAM/PNAF) or an oil vehicle (VEH) from gestational days 16 to 18 were tested for a suite of sex-specific behaviours.
PNAM showed a reduction in their mounting capabilities, however, most of PNAM where able to reach ejaculation by the end of the test similar to the VEH control males. In contrast, PNAF exhibited a significant impairment in the female-typical sexual behaviour, lordosis. Interestingly, while neuronal activation was largely similar between PNAF and VEH females, impaired lordosis behaviour in PNAF was unexpectedly associated with decreased neuronal activation in the dorsomedial hypothalamic nucleus (DMH).
Taken together, these data link prenatal androgen exposure that drives a PCOS-like phenotype with altered sexual behaviours in both sexes.
多囊卵巢综合征（PCOS）是全球最常见的不孕疾病，其典型特征是循环雄激素水平升高、排卵障碍和多囊卵巢形态。多囊卵巢综合征妇女也报告有性功能障碍，包括性欲下降和性满足感增加。这些性困难的起源在很大程度上仍未确定。为了研究多囊卵巢综合征患者性功能障碍的潜在生物学起源，我们询问了多囊卵巢综合征的特征明确的、产前雄激素化（PNA）小鼠模型是否表现出改变的性行为，以及与女性性行为相关的中枢脑回路是否受到不同的调节。由于多囊卵巢综合征妇女的兄弟中报告存在男性多囊卵巢综合征等效物，我们还研究了母体雄激素过多对男性同胞性行为的影响。
从妊娠第 16 天至第 18 天接受二氢睾酮（PNAM/PNAF）或油载体（VEH）处理的母鼠的成年雄性和雌性后代接受了一系列特定于性别的行为测试。
PNAM 的交配能力下降，但大多数 PNAM 能够在测试结束时达到射精，类似于 VEH 对照雄性。相比之下，PNAF 表现出明显的雌性典型性行为（发情）障碍。有趣的是，尽管 PNAF 和 VEH 雌性之间的神经元激活大致相似，但 PNAF 中发情行为受损与背内侧下丘脑核（DMH）中的神经元激活减少意外相关。
综上所述，这些数据将导致多囊卵巢综合征样表型的产前雄激素暴露与两性改变的性行为联系起来。
