Introduction. Altered signalling of androgens, anti-Mullerian hormone or transforming growth factor beta (TGFβ1) during fetal development has been implicated in the predisposition to polycystic ovary syndrome (PCOS) in later life, in addition to genetic predisposition. In fetal ovarian fibroblasts, we have shown that TGFβ1 regulates androgen signalling and seven genes located in loci associated with PCOS. The complex symptomology of PCOS indicates that it likely involves many different organs.
Aim. To identify the relationships between TGFb signalling molecules and PCOS candidate genes in different tissues associated with PCOS.
Methods. 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 4-20 weeks of gestation and postnatally. We also examined the correlations between gene expression of TGFβ signalling molecules and PCOS candidate genes.
Key results. TGFb signalling molecules were dynamically expressed in most tissues prenatally or/and postnatally. FBN3, a PCOS candidate gene involved in TGFb signalling, was expressed during fetal development in all tissues. The PCOS candidate genes HMGA2, YAP1 and RAD50 correlated positively (P < 0.01) with most TGFβ signalling molecules in at least four fetal tissues, and specifically with TGFBR1 in six out of the seven tissues examined.
Conclusion. This study suggests that possible crosstalk occurs between genes in loci associated with PCOS and TGFβ signalling molecules in multiple tissues, particularly during fetal development. Thus, alteration in TGFβ signalling during fetal development could affect many tissues contributing to the multiple symptomologies and phenotypes of PCOS in later life.