Dryad
Published November 1, 2019 | Version v1
Dataset Open

Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome

Description

The effects of how obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring are unclear. We found that daughters of PCOS mothers are more likely to be diagnosed with PCOS in a Swedish nationwide register-based cohort and a clinical case-control study from Chile. Further, female mice (F0) with PCOS-like traits induced by late gestation injection of dihydrotestosterone, with and without obesity, produced female F1–F3 offspring with a PCOS-like reproductive and metabolic phenotypes. Sequencing of single MII 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 PCOS mothers and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.

Notes

Funding provided by: SRP in Diabetes at Karolinska Institutet
Crossref Funder Registry ID:
Award Number:

Funding provided by: Karolinska Institutet KID funding
Crossref Funder Registry ID:
Award Number:

Funding provided by: Swedish Association of Medical Research (SSMF)
Crossref Funder Registry ID:
Award Number:

Funding provided by: Åke Wiberg Foundation
Crossref Funder Registry ID:
Award Number:

Funding provided by: Regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet
Crossref Funder Registry ID:
Award Number:

Funding provided by: National Fund for Scientific and Technological Development (FONDECYT)
Crossref Funder Registry ID:
Award Number: 1071007

Funding provided by: National Fund for Scientific and Technological Development (FONDECYT)
Crossref Funder Registry ID:
Award Number: 1151531 to TS-P

Funding provided by: FONDECYT
Crossref Funder Registry ID:
Award Number: 1181798 to MM

Funding provided by: Swedish Medical Research Council
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100004359
Award Number: 2014-2775

Funding provided by: Swedish Medical Research Council
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100004359
Award Number: 2018-02435 ESV

Funding provided by: Swedish Medical Research Council
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100004359
Award Number: 2014-2870 QD

Funding provided by: Swedish Medical Research Council
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100004359
Award Number: 2018-02119 MR

Funding provided by: Novo Nordisk Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100011747
Award Number: NNF16OC0020744

Funding provided by: Novo Nordisk Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100011747
Award Number: NNF17OC0026724

Funding provided by: Novo Nordisk Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100011747
Award Number: NNF18OC0033992

Funding provided by: Novo Nordisk Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100011747
Award Number: NNF19OC0056647

Files

Risal_SourceData__Extended_Data_Fig._7bdfhjl.pdf

Files (58.0 MB)

Name Size
md5:2d20fbbf186a1c74c041b37c1ef9aa7d
32.0 kB Download
md5:908e3d502420b5d093d7b8d9a573689b
13.6 kB Download
md5:b729bdb5e411b071d9d0f848bc70f0e7
18.3 kB Download
md5:7dc120d4a33c3b71642d083313ebbce4
21.1 kB Download
md5:45c82a29e2f9db0686310d6a32332938
108.6 kB Download
md5:48708bd3faaa09e943d8d3fd59576f31
71.0 kB Download
md5:f532dc7035294610d408304b8165449a
19.3 kB Download
md5:b13f78717c63c1a0a213cb05af4cf3b0
36.3 MB Preview Download
md5:6910662bb43e916cbf1e4435e499c8d6
36.6 kB Download
md5:aa3259f5a42eaadfe83a472f30ee42e9
23.0 kB Download
md5:fd62983d7e65e92e39845f330c55df43
5.7 MB Download
md5:5f2c3891b110aa3c3ebdfb079a2f84db
10.2 MB Preview Download
md5:affcf2a427858438affd8145221c497d
5.2 MB Download
md5:a8a8d095c887484c22addd9e77b2783b
229.1 kB Download