Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, China.
Biol Reprod. 2017 Jan 1;97(6):873-882. doi: 10.1093/biolre/iox140.
To elucidate whether the endometriotic cells of endometriomas synthesize transforming growth factor beta1 (TGF-beta1) and understand how it affects surrounding ovarian tissue. We collected biopsies of the cystic walls from 42 endometriomas and 29 mature teratomas and compared mRNA and protein expression of fibrosis-related factors between the cystic walls. Then we detected TGFB1 mRNA synthesis in endometriomas, and tested TGF-beta1 fibrotic effect in vitro. Moreover, we verified the expression of Smad2/3 signaling components in the endometriotic cystic wall in order to understand whether TGF-beta1/Smad signaling is involved in fibrosis formation of the tissue surrounding endometriomas. The cystic walls from endometriomas demonstrated severe adhesion to ovarian tissue and obvious fibrosis compared with the mature teratomas, which was proven by the increased mRNA expression of fibrotic markers. Additionally, TGFB1 was obviously expressed in the endometriotic cystic wall, and total TGFB1 protein was significantly higher in the cystic walls of endometriomas than mature teratomas. Interestingly, TGFB1 mRNA was confirmed to be specifically synthesized in the endometriotic loci through fluorescence in situ hybridization. Cultured endometriomas derived stromal cells showed obvious fibrosis after exposed to TGF-beta1. Furthermore, components of the TGF-beta1/Smad pathway such as Smad2, Smad3, Smad4, and their phosphorylated forms were also expressed in the same location as TGF-beta1, TGF-beta receptor1, and fibrotic factors expressed in the endometriotic cystic walls. In summary, endometriotic cells of endometriomas synthesize TGF-beta1 leading to fibrosis and adhesion to ovarian tissues, and TGF-beta1/Smad signaling pathway is involved in this pathological process.
为了阐明卵巢子宫内膜异位囊肿(内异症)中的异位内膜细胞是否合成转化生长因子-β1(TGF-β1)以及了解其如何影响周围卵巢组织。我们收集了 42 个内异症囊肿和 29 个成熟畸胎瘤的囊壁活检,并比较了囊壁中纤维化相关因子的 mRNA 和蛋白表达。然后我们检测了内异症中 TGFB1 mRNA 的合成,并在体外检测了 TGF-β1 的纤维化作用。此外,我们验证了子宫内膜异位症囊壁中 Smad2/3 信号成分的表达,以了解 TGF-β1/Smad 信号是否参与内异症周围组织纤维化的形成。与成熟畸胎瘤相比,内异症囊肿的囊壁与卵巢组织严重粘连并有明显纤维化,这一点通过纤维化标志物的 mRNA 表达增加得到证实。此外,TGFB1 在子宫内膜异位症囊壁中明显表达,内异症囊肿壁中的总 TGFB1 蛋白明显高于成熟畸胎瘤。有趣的是,通过荧光原位杂交证实 TGFB1 mRNA 特异性在内异症部位合成。暴露于 TGF-β1 后,培养的内异症来源的基质细胞表现出明显的纤维化。此外,TGF-β1/Smad 通路的成分,如 Smad2、Smad3、Smad4 及其磷酸化形式,也在内异症囊壁中与 TGF-β1、TGF-β 受体 1 和纤维化因子表达的相同位置表达。总之,内异症中的异位内膜细胞合成 TGF-β1 导致纤维化和与卵巢组织的粘连,TGF-β1/Smad 信号通路参与这一病理过程。