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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome.

Journal article
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
Published in Nature medicine
Volume 25
Issue 12
Pages 1894-1904
ISSN 1546-170X
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Physiology
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 1894-1904
Language en
Links dx.doi.org/10.1038/s41591-019-0666-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Endocrinology

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.

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