Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/126181
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Type: Journal article
Title: Could perturbed fetal development of the ovary contribute to the development of polycystic ovary syndrome in later life?
Author: Hartanti, M.D.
Rosario, R.
Hummitzsch, K.
Bastian, N.A.
Hatzirodos, N.
Bonner, W.M.
Bayne, R.A.
Irving-Rodgers, H.F.
Anderson, R.A.
Rodgers, R.J.
Citation: PLoS One, 2020; 15(2):e0229351-1-e0229351-24
Publisher: Plos One
Issue Date: 2020
ISSN: 1932-6203
1932-6203
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Responsibility: 
Monica D. Hartanti ... Katja Hummitzsch, Nicole A. Bastian, Nicholas Hatzirodos, Wendy M. Bonner ... Raymond J. Rodgers ... et al.
Abstract: Polycystic ovary syndrome (PCOS) affects around 10% of young women, with adverse consequences on fertility and cardiometabolic outcomes. PCOS appears to result from a genetic predisposition interacting with developmental events during fetal or perinatal life. We hypothesised that PCOS candidate genes might be expressed in the fetal ovary when the stroma develops; mechanistically linking the genetics, fetal origins and adult ovarian phenotype of PCOS. In bovine fetal ovaries (n = 37) of 18 PCOS candidate genes only SUMO1P1 was not expressed. Three patterns of expression were observed: early gestation (FBN3, GATA4, HMGA2, TOX3, DENND1A, LHCGR and FSHB), late gestation (INSR, FSHR, and LHCGR) and throughout gestation (THADA, ERBB4, RAD50, C8H9orf3, YAP1, RAB5B, SUOX and KRR1). A splice variant of FSHB exon 3 was also detected early in the bovine ovaries, but exon 2 was not detected. Three other genes, likely to be related to the PCOS aetiology (AMH, AR and TGFB1I1), were also expressed late in gestation. Significantly within each of the three gene groups, the mRNA levels of many genes were highly correlated with each other, despite, in some instances, being expressed in different cell types. TGFβ is a well-known stimulator of stromal cell replication and collagen synthesis and TGFβ treatment of cultured fetal ovarian stromal cells inhibited the expression of INSR, AR, C8H9orf3 and RAD50 and stimulated the expression of TGFB1I1. In human ovaries (n = 15, < 150 days gestation) many of the same genes as in bovine (FBN3, GATA4, HMGA2, FSHR, DENND1A and LHCGR but not TOX3 or FSHB) were expressed and correlated with each other. With so many relationships between PCOS candidate genes during development of the fetal ovary, including TGFβ and androgen signalling, we suggest that future studies should determine if perturbations of these genes in the fetal ovary can lead to PCOS in later life.
Keywords: Ovaries; polycystic ovary syndrome; gene expression; fibroblasts; androgens; RNA extraction; genome-wide association studies; sequence alignment
Rights: © 2020 Hartanti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI: 10.1371/journal.pone.0229351
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