Hyperandrogenic disorders, such as polycystic ovary syndrome, are often associated with metabolic disruptions such as insulin resistance and hyperinsulinemia. Studies in sheep, a precocial model of translational relevance, provide evidence that exposure to excess testosterone during days 30–90 of gestation (the sexually dimorphic window where males naturally experience elevated androgens) programs insulin resistance and hyperinsulinemia in female offspring. Extending earlier findings that adverse effects of testosterone excess are evident in fetal day 90 pancreas, the end of testosterone treatment, the present study provides evidence that transcriptomic and phenotypic effects of testosterone excess on female pancreas persist after cessation of treatment, suggesting lasting organizational changes, and induce a male-like phenotype in female pancreas. These findings demonstrate that the female pancreas is susceptible to programmed masculinization during the sexually dimorphic window of fetal development and shed light on underlying connections between hyperandrogenism and metabolic homeostasis.

中文翻译：

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发育规划：睾酮过量使绵羊雌性胰腺转录组和功能男性化

高雄激素性疾病，例如多囊卵巢综合征，通常与代谢紊乱有关，例如胰岛素抵抗和高胰岛素血症。对绵羊（一种转化相关性的早熟模型）的研究提供了证据，表明在妊娠 30-90 天（雄性自然经历升高的雄激素的性别二态性窗口）期间接触过量的睾酮会导致雌性后代的胰岛素抵抗和高胰岛素血症。早期发现睾酮过量的不利影响在胎儿第 90 天的胰腺（睾酮治疗结束）中很明显，本研究提供了证据表明睾酮过量对女性胰腺的转录组学和表型影响在治疗停止后持续存在，表明持久的组织变化，并在女性胰腺中诱导类似男性的表型。这些发现表明，在胎儿发育的性别二态性窗口期间，女性胰腺容易受到程序性男性化的影响，并揭示了高雄激素血症和代谢稳态之间的潜在联系。