瑞典卡罗林斯卡学院Elisabet Stener-Victorin、Qiaolin Deng等研究人员合作揭示了产前雄激素暴露对多囊卵巢综合征的跨代影响。这一研究成果2019年12月2日在线发表于国际学术期刊《自然—医学》。

多囊卵巢综合征（PCOS）妇女的肥胖和雄激素水平升高如何影响其后代尚不清楚。

在一项来自瑞典全国范围内基于登记的队列研究和一项来自智利的临床病例对照研究中，研究人员发现患有PCOS的母亲的女儿更有可能被诊断出患有PCOS。此外，雌性小鼠（F0）的妊娠后期注射双氢睾丸激素导致PCOS样特征，无论是否患有肥胖，都产生具有PCOS样生殖和代谢表型的雌性F1-F3后代。F1-F3后代的单个中期II卵母细胞测序揭示了各个世代中共同且独特的基因表达改变。值得注意的是，在病例对照研究中，女儿的血样和与PCOS无关的女性的血清样本中也有四个基因差异表达。这一发现为患有PCOS母亲的雌性后代提供了跨代作用的证据，并确定了可能的候选基因，以预测后代的PCOS表型。

附：英文原文

Title: Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome

Author: Sanjiv Risal, Yu Pei, Haojiang Lu, Maria Manti, Romina Fornes, Han-Pin Pui, Zhiyi Zhao, Julie Massart, Claes Ohlsson, Eva Lindgren, Nicolas Crisosto, Manuel Maliqueo, Barbara Echibur, Amanda Ladrn de Guevara, Teresa Sir-Petermann, Henrik Larsson, Mina A. Rosenqvist, Carolyn E. Cesta, Anna Benrick, Qiaolin Deng, Elisabet Stener-Victorin

Issue&Volume: 2019-12-02

Abstract: 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.

DOI: 10.1038/s41591-019-0666-1

Source: https://www.nature.com/articles/s41591-019-0666-1