Could perturbed fetal development of the ovary contribute to the development of polycystic ovary syndrome in later life?
| Autor: | Richard A. Anderson, Nicholas Hatzirodos, Raymond J. Rodgers, Katja Hummitzsch, Roseanne Rosario, Wendy M. Bonner, Nicole A Bastian, Monica Dwi Hartanti, Helen F. Irving-Rodgers, Rosemary A. L. Bayne |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Candidate gene endocrine system diseases Gene Expression Biochemistry FSHB Fetal Development Database and Informatics Methods 0302 clinical medicine Animal Cells Pregnancy Genes Regulator Medicine and Health Sciences Connective Tissue Cells 030219 obstetrics & reproductive medicine Multidisciplinary Gene Expression Regulation Developmental Genomics Polycystic ovary Phenotype Ovaries Oncology Connective Tissue Androgens Medicine Female Anatomy Cellular Types Sequence Analysis Research Article Polycystic Ovary Syndrome Adult endocrine system Stromal cell Genotype Bioinformatics medicine.drug_class Science Biology Polymorphism Single Nucleotide Andrology 03 medical and health sciences Extraction techniques Genetics Genome-Wide Association Studies Genetic predisposition medicine Animals Humans Genetic Predisposition to Disease Fetus Ovary Reproductive System Biology and Life Sciences Cancers and Neoplasms Computational Biology Human Genetics Cell Biology Fibroblasts Genome Analysis Androgen Hormones RNA extraction Research and analysis methods Biological Tissue 030104 developmental biology Cattle Stromal Cells Gynecological Tumors Sequence Alignment Biomarkers Genome-Wide Association Study |
| Zdroj: | Hartanti, M D, Rosario, R, Hummitzsch, K, Bastian, N A, Hatzirodos, N, Bonner, W, Bayne, R A, Irving-Rodgers, H F, Anderson, R & Rodgers, R J 2020, ' Could perturbed fetal development of the ovary contribute to the development of polycystic ovary syndrome in later life? ', PLoS ONE . https://doi.org/10.1371/journal.pone.0229351 PLoS ONE, Vol 15, Iss 2, p e0229351 (2020) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0229351 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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