Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome.

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.

• Authors: Sanjiv Risal, Yu Pei, Haojiang Lu, Maria Manti, Romina Fornes, Han-Pin Pui, Zhiyi Zhao, Julie Massart, Claes Ohlsson, Eva Lindgren, Nicolas Crisosto, Manuel Maliqueo, Barbara Echiburú, Amanda Ladrón de Guevara, Teresa Sir-Petermann, Henrik Larsson, Mina A Rosenqvist, Carolyn E Cesta, Anna Benrick, Qiaolin Deng, Elisabet Stener-Victorin
• Journal: Nature medicine (Nat Med) Vol. 25 Issue 12 Pg. 1894-1904 (12 2019) ISSN: 1546-170X [Electronic] United States
• PMID: 31792459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens

Topics

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