期刊
NATURE MEDICINE
卷 25, 期 12, 页码 1894-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-019-0666-1
关键词
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资金
- Swedish Medical Research Council [2014-2775, 2018-02435, 2014-2870, 2018-02119]
- Novo Nordisk Foundation [NNF17OC0026724, NNF18OC0033992, NNF19OC0056647]
- Strategic Research Program in Diabetes at the Karolinska Institutet
- Adlerbertska Research Foundation
- Karolinska Institutet KID funding
- Swedish Association of Medical Research
- Ake Wiberg Foundation
- Stockholm County Council
- Karolinska Institutet
- Royal Swedish Academy of Sciences (KVA) [BS2015-0012]
- National Fund for Scientific and Technological Development (FONDECYT) [1071007, 1151531]
- FONDECYT [1181798]
- Vinnova [2018-02435] Funding Source: Vinnova
- Swedish Research Council [2018-02435, 2018-02119] Funding Source: Swedish Research Council
- Formas [2018-02435] Funding Source: Formas
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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