Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome.
Nat Med, 2019/12;25(12):1894-1904.
Risal S[1], Pei Y[1, 2], Lu H[1], Manti M[1], Fornes R[1], Pui HP[1], Zhao Z[1, 3], Massart J[4], Ohlsson C[5], Lindgren E[1], Crisosto N[6, 7], Maliqueo M[6], Echiburú B[6], Ladrón de Guevara A[6], Sir-Petermann T[6], Larsson H[8, 9], Rosenqvist MA[8], Cesta CE[10], Benrick A[11, 12], Deng Q[13, 14], Stener-Victorin E[15]
Affiliations
PMID: 31792459DOI: 10.1038/s41591-019-0666-1
Impact factor: 87.241
Abstract
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.
MeSH terms
Androgens; Animals; Cohort Studies; Female; Gene Expression Regulation, Developmental; Humans; Mice; Nuclear Family; Obesity, Maternal; Oocytes; Phenotype; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Single-Cell Analysis
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