Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome

The effects of how obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring are unclear. We found that daughters of PCOS mothers are more likely to be diagnosed with PCOS in a Swedish nationwide register-based cohort and a clinical case-control study from Chile. Further, female mice (F0) with PCOS-like traits induced by late gestation injection of dihydrotestosterone, with and without obesity, produced female F1–F3 offspring with a PCOS-like reproductive and metabolic phenotypes. Sequencing of single MII 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 PCOS mothers and identify possible candidate genes for the prediction of a PCOS phenotype in future generations. Transcriptomic profiles of mice MII oocytes across generations