Browsing by Author "Risal, Sanjiv"
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Publication Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome(2023) Risal, Sanjiv; Li, Congru; Luo, Qing; Fornes, Romina; Lu, Haojiang; Eriksson, Gustaw; Manti, Maria; Ohlsson, Claes; Lindgren, Eva; Crisosto, Nicólas; Maliqueo, Manuel; Echiburú, Barbara; Recabarren, Sergio; Sir Petermann, Teresa; Benrick, Anna; Brusselaers, Nele; Qiao, Jie; Deng, Qiaolin; Stener-Victorin, ElisabetThe 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.