Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome

Cell Rep Med. 2023 May 16;4(5):101035. doi: 10.1016/j.xcrm.2023.101035. Epub 2023 May 5.


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.

Keywords: adipose tissue; male offspring; male offspring to male germline; maternal hyperandrogenism; maternal obesity; polycystic ovary syndrome; small non-coding RNAs; sperm; transgenerational transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Mice
  • Obesity / genetics
  • Polycystic Ovary Syndrome* / genetics
  • Pregnancy
  • Reproduction / genetics
  • Semen