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.