How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.

中文翻译：

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产前雄激素暴露和多囊卵巢综合征的跨代易感性。

多囊卵巢综合征 (PCOS) 女性的肥胖和雄激素水平升高如何影响其后代尚不清楚。在瑞典全国登记的队列和智利的临床病例对照研究中，我们发现患有 PCOS 的母亲的女儿更有可能被诊断出患有 PCOS。此外，由孕晚期注射双氢睾酮诱导的具有 PCOS 样特征的雌性小鼠 (F0)，无论是否肥胖，都产生了具有 PCOS 样生殖和代谢表型的雌性 F1-F3 后代。来自 F1-F3 后代的单个中期 II 卵母细胞的测序揭示了所有世代的共同和独特的基因表达改变。值得注意的是，病例对照研究中女儿和不相关的多囊卵巢综合征女性的血清样本中也有四个基因存在差异表达。