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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
Open accessAbstract
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 (F 0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F 1-F 3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F 1-F 3 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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Metadata
- Authors
- Risal, S., Pei, Y., Lu, H., Manti, M., Fornes, R., Pui, H.-P., Zhao, Z., Massart, J., Ohlsson, C., Lindgren, E., Crisosto, N., Maliqueo, M., Echiburú, B., Ladrón de Guevara, A., Sir-Petermann, T., Larsson, H., Rosenqvist, M. A., Cesta, C. E., Benrick, A., Deng, Q., & Stener-Victorin, E.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- University of Gothenburg (SE)
- University of Chile (CL)
- Örebro University (SE)
- University of Skövde (SE)
- Corresponding author
- Deng, Qiaolin
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-12
- Volume
- 25
- Issue
- 12
- Pages
- 1894-1904
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2989769687
- Cited by
- 356
- References
- 73
- Citations by year
- 2026: 39 · 2025: 61 · 2024: 60 · 2023: 58 · 2022: 60 · 2021: 46 · 2020: 29 · 2019: 2
- FWCI
- 32.74
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- www.springer.com/tdm (vor)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- DRYAD (public-domain)
- Funders
- Åke Wiberg Stiftelse
- Vetenskapsrådet (2014-02775, 2014-2870 QD, 2018-02435 ESV, 2018-02119 MR)
- Novo Nordisk Fonden (NNF14OC0010513, NNF18OC0033898, NNF13OC0005785, NNF18OC0033992, NNF19OC0056647)
- Novo Nordisk Foundation Center for Basic Metabolic Research (NNF19OC0056647, NNF16OC0020744, NNF17OC0026724, NNF18OC0033992)
- Fondo Nacional de Desarrollo Científico y Tecnológico (1181798 to MM)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Keywords
- polycystic ovary syndrome, transgenerational effects, prenatal androgen exposure, dihydrotestosterone, maternal obesity, female offspring, oocyte gene expression, candidate genes, reproductive phenotypes, metabolic phenotypes, epigenetics
- MeSH terms
- Pregnancy in Obesity, Androgens, Animals, Female, Humans, Nuclear Family, Oocytes, Phenotype, Polycystic Ovary Syndrome, Pregnancy, Prenatal Exposure Delayed Effects, Cohort Studies, Gene Expression Regulation, Developmental, Mice, Single-Cell Analysis
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