Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome

Nat Med. 2019 Dec;25(12):1894-1904. doi: 10.1038/s41591-019-0666-1. Epub 2019 Dec 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism*
  • Animals
  • Cohort Studies
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Mice
  • Nuclear Family
  • Obesity, Maternal / blood
  • Obesity, Maternal / genetics*
  • Obesity, Maternal / metabolism
  • Obesity, Maternal / physiopathology
  • Oocytes / immunology
  • Oocytes / metabolism*
  • Phenotype
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / diagnosis
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / physiopathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / diagnosis
  • Prenatal Exposure Delayed Effects / genetics*
  • Prenatal Exposure Delayed Effects / physiopathology
  • Single-Cell Analysis


  • Androgens