Abstract：
Context 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. Aims To identify the relationships between TGFβ 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 to 20weeks of gestation and postnatally. We also examined the correlations between gene expression of TGFβ signalling molecules and PCOS candidate genes. Key results 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 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 TGFβ signalling molecules in multiple tissues, particularly during foetal development. Implications Thus, alteration in TGFβ signalling during foetal development could affect many tissues contributing to the multiple phenotypes of PCOS in later life.
摘要：
上下文改变了雄激素的信号，胎儿发育过程中的抗苗勒管激素或转化生长因子β（TGFβ）与晚年多囊卵巢综合征（PCOS）的易感性有关，除了它的遗传倾向。在胎儿卵巢成纤维细胞中，已显示TGFβ1调节雄激素信号传导和位于与PCOS相关的基因座中的七个基因。由于PCOS表现出无数的症状，它可能涉及许多不同的器官。目的探讨TGFβ信号分子与PCOS相关不同组织中PCOS候选基因的关系。方法采用RNA测序数据,我们检查了TGFβ信号分子在人卵巢中的表达模式，睾丸,心,肝脏,肾,脑组织,妊娠4至20周和出生后的小脑。我们还检查了TGFβ信号分子的基因表达与PCOS候选基因之间的相关性。关键结果TGFβ信号分子在产前和/或产后在大多数组织中动态表达。FBN3,参与TGFβ信号传导的PCOS候选基因，在胎儿发育过程中在所有组织中表达。PCOS候选基因HMGA2、YAP1、和RAD50显着相关（PTGFBR1在所检查的七个组织中的六个中。结论本研究提示多囊卵巢综合征相关基因位点与多种组织中TGFβ信号分子之间可能发生串扰,特别是在胎儿发育期间。因此，胎儿发育过程中TGFβ信号的改变可能会影响许多组织，从而在以后的生活中导致PCOS的多种表型。
