Expression of transforming growth factor ß signalling molecules and their correlations with genes in loci linked to polycystic ovary syndrome in human foetal and adult tissues.

ABSTRACT

Context Altered signalling of androgens, anti-Müllerian hormone or transforming growth factor beta (TGFß) 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, TGFß1 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. Aims To identify the relationships between TGFß signalling molecules and PCOS candidate genes in different tissues associated with PCOS. Methods Using RNA sequencing data, we examined the expression patterns of TGFß signalling molecules in the human ovary, testis, heart, liver, kidney, brain tissue, and cerebellum from 4 to 20weeks of gestation and postnatally. We also examined the correlations between gene expression of TGFß signalling molecules and PCOS candidate genes. Key results TGFß signalling molecules were dynamically expressed in most tissues prenatally and/or postnatally. FBN3 , a PCOS candidate gene involved in TGFß signalling, was expressed during foetal development in all tissues. The PCOS candidate genes HMGA2, YAP1 , and RAD50 correlated significantly (P TGFBR1 in six out of the seven tissues examined. Conclusions This study suggests that possible crosstalk occurs between genes in loci associated with PCOS and TGFß signalling molecules in multiple tissues, particularly during foetal development. Implications Thus, alteration in TGFß signalling during foetal development could affect many tissues contributing to the multiple phenotypes of PCOS in later life.