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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
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2019 (Engelska)Ingår i: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, nr 12, s. 1894-1904Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2019. Vol. 25, nr 12, s. 1894-1904
Nationell ämneskategori
Medicin och hälsovetenskap Fysiologi
Forskningsämne
Translationell medicin TRIM
Identifikatorer
URN: urn:nbn:se:his:diva-18005DOI: 10.1038/s41591-019-0666-1ISI: 000500824900033PubMedID: 31792459Scopus ID: 2-s2.0-85075981179OAI: oai:DiVA.org:his-18005DiVA, id: diva2:1377610
Tillgänglig från: 2019-12-12 Skapad: 2019-12-12 Senast uppdaterad: 2020-01-29Bibliografiskt granskad

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