Yang Xiao-Jun, Yang Jian, Liu Zhen, Yang Gang, Shen Zong-Ji
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.
J Cell Mol Med. 2015 Feb;19(2):452-62. doi: 10.1111/jcmm.12427. Epub 2014 Nov 11.
Women with endometriosis (EMs) have unexplained infertility. The recently identified telocytes (TCs) might participate in the maintenance of structural and functional integrity of oviduct tissue, but so far the involvement of TCs in EMs-affected oviduct tissue and potential impact on fertility capacity remain unknown. By an integrated technique of haematoxylin and eosin staining, in situ immunohistochemistry and double-labelled immunofluorescence staining and electron microscopy approach, TCs were studied in the autotransplantation Sprague-Dawley rat model of EMs-affected oviduct tissue and in sham control, respectively, together with determination of iNOS, COX-2, LPO and estradiol. TCs were found in perivascular connective tissue and smooth muscle bundles in sham oviduct, with typical ultrastructural features (a slender piriform/spindle/triangular cell body, and one or more extremely long prolongations, emerged from cell bodies and extend to various directions), and specific immunophenotype of CD34-positive/vimentin-positive/c-kit-negative. However, in EMs-affected oviduct tissue (grade III), extensive ultrastructural damage (degeneration, discontinue, dissolution and destruction), significant decrease or loss of TCs and interstitial fibrosis were observed, together with elevated level of iNOS, COX-2, LPO and estradiol, thus suggestive of inflammation and ischaemia-induced TCs damage. Based on TCs distribution and intercellular connections, we proposed that such damage might be involved in structural and functional abnormalities of oviduct, such as attenuated intercellular signalling and oviduct contractility, impaired immunoregulation and stem cell-mediated tissue repair, 3-D interstitial architectural derangement and tissue fibrosis. Therefore, TCs damage might provide a new explanation and potential target for EMs-induced tubal damage and fertility disorders.
患有子宫内膜异位症(EMs)的女性存在不明原因的不孕。最近发现的间充质干细胞(TCs)可能参与输卵管组织结构和功能完整性的维持,但迄今为止,TCs在受EMs影响的输卵管组织中的作用以及对生育能力的潜在影响仍不清楚。通过苏木精和伊红染色、原位免疫组化、双标免疫荧光染色以及电子显微镜技术相结合的方法,分别在受EMs影响的输卵管组织的自体移植Sprague-Dawley大鼠模型和假手术对照组中研究了TCs,并测定了诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)、脂质过氧化(LPO)和雌二醇的水平。在假手术组输卵管的血管周围结缔组织和平滑肌束中发现了TCs,其具有典型的超微结构特征(细胞体细长,呈梨形/纺锤形/三角形,有一个或多个极长的突起,从细胞体发出并向各个方向延伸),以及CD34阳性/波形蛋白阳性/c-kit阴性的特定免疫表型。然而,在受EMs影响的输卵管组织(III级)中,观察到广泛的超微结构损伤(变性、中断、溶解和破坏)、TCs显著减少或缺失以及间质纤维化,同时iNOS、COX-2、LPO和雌二醇水平升高,提示炎症和缺血诱导的TCs损伤。基于TCs的分布和细胞间连接,我们认为这种损伤可能与输卵管的结构和功能异常有关,如细胞间信号传导减弱和输卵管收缩力下降、免疫调节受损以及干细胞介导的组织修复受损、三维间质结构紊乱和组织纤维化。因此,TCs损伤可能为EMs引起的输卵管损伤和生育障碍提供新的解释和潜在靶点。