PCOSが将来世代の男性の健康に与える影響について(How PCOS can affect the health of future generations of men)


2023-05-05 カロリンスカ研究所(KI)



多嚢胞性卵巣症候群の男性子孫における生殖機能障害および代謝機能障害の世代間伝達について Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome

Sanjiv Risal,Congru Li,Qing Luo,Romina Fornes,Haojiang Lu,Gustaw Eriksson,Maria Manti,Claes Ohlsson,Eva Lindgren,Nicolas Crisosto,Manuel Maliqueo,Barbara Echiburú,Sergio Recabarren,Teresa Sir Petermann,Anna Benrick,Nele Brusselaers,Jie Qiao,Qiaolin Deng,Elisabet Stener-Victorin
Cell Reports Medicine  Published:May 05, 2023

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•PCOS-sons are often obese and have dyslipidemia
•miRNAs altered in the serum of PCOS-sons and women with PCOS targets PCOS-risk genes
•Small RNAs present in sperm imply transgenerational transmission of phenotype in mice
•Shared miRNAs between mouse sperm of F1–F3 generations and human serum are revealed


The transgenerational maternal effects of polycystic ovary syndrome (PCOS) in female progeny are being revealed. As there is evidence that a male equivalent of PCOS may exists, we ask whether sons born to mothers with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a register-based cohort and a clinical case-control study, we find that PCOS-sons are more often obese and dyslipidemic. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in first-generation (F1) male offspring are passed down to F3. Sequencing of F1–F3 sperm reveals distinct differentially expressed (DE) small non-coding RNAs (sncRNAs) across generations in each lineage. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism, strengthening the translational relevance and highlighting a previously underappreciated risk of transmission of reproductive and metabolic dysfunction via the male germline.