Expression of transforming growth factor β signalling molecules and their correlations with genes in loci linked to polycystic ovary syndrome in human foetal and adult tissues
Rafiatu Azumah A , Katja Hummitzsch A , Richard A. Anderson B and Raymond J. Rodgers
A *
A
B
Abstract
Altered signalling of androgens, anti-Müllerian hormone or transforming growth factor beta (TGFβ) during foetal development have been implicated in the predisposition to polycystic ovary syndrome (PCOS) in later life, aside from its genetic predisposition. In foetal ovarian fibroblasts, TGFβ1 has been shown to regulate androgen signalling and seven genes located in loci associated with PCOS. Since PCOS exhibits a myriad of symptoms, it likely involves many different organs.
To identify the relationships between TGFβ signalling molecules and PCOS candidate genes in different tissues associated with PCOS.
Using RNA sequencing data, we examined the expression patterns of TGFβ signalling molecules in the human ovary, testis, heart, liver, kidney, brain tissue, and cerebellum from 4 to 20 weeks of gestation and postnatally. We also examined the correlations between gene expression of TGFβ signalling molecules and PCOS candidate genes.
TGFβ signalling molecules were dynamically expressed in most tissues prenatally and/or postnatally. FBN3, a PCOS candidate gene involved in TGFβ signalling, was expressed during foetal development in all tissues. The PCOS candidate genes HMGA2, YAP1, and RAD50 correlated significantly (P < 0.01) with most TGFβ signalling molecules in at least four foetal tissues, and specifically with TGFBR1 in six out of the seven tissues examined.
This study suggests that possible crosstalk occurs between genes in loci associated with PCOS and TGFβ signalling molecules in multiple tissues, particularly during foetal development.
Thus, alteration in TGFβ signalling during foetal development could affect many tissues contributing to the multiple phenotypes of PCOS in later life.
Keywords: adult, brain, fetus, gene expression, heart, kidney, liver, ovary, polycystic ovary syndrome, testis, TGFβ.
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