Nakayama Jun, Aoki Daisuke, Suga Tomoaki, Akama Tomoya O, Ishizone Satoshi, Yamaguchi Hirohito, Imakawa Kazuhiko, Nadano Daita, Fazleabas Asgerally T, Katsuyama Tsutomu, Nozawa Shiro, Fukuda Michiko N
Departments of Pathology, Internal Medicine, Surgery, and Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Am J Pathol. 2003 Dec;163(6):2211-9. doi: 10.1016/S0002-9440(10)63579-1.
Trophinin, tastin, and bystin have been identified as molecules potentially involved in human embryo implantation. Both trophoblasts and endometrial epithelial cells express trophinin, which mediates apical cell adhesion through homophilic trophinin-trophinin binding. We hypothesized that trophinin's function in embryo implantation is unique to humans and investigated the expression of trophinin, tastin, and bystin in ectopic pregnancy, a condition unique to humans. In tubal pregnancies, high levels of all three were found in both trophoblasts and fallopian tubal epithelia. Trophinin expression in maternal cells was particularly high in the area adjacent to the trophoblasts, whereas trophinin was barely detectable in intact fallopian tubes from women with in utero pregnancies or without pregnancies. When explants of intact fallopian tube were incubated with the human chorionic gonadotrophin (hCG), trophinin expression was enhanced in epithelial cells. Since the trophectoderm of the human blastocyst secretes hCG before and after implantation, these results suggest that hCG from the human embryo induces trophinin expression by maternal cells. As both beta-subunit of hCG and trophinin genes have diverged in mammals, the present study suggests a unique role of hCG and trophinin in human embryo implantation, including the pathogenesis of ectopic pregnancy.
滋养蛋白、味觉蛋白和附睾蛋白已被确定为可能参与人类胚胎着床的分子。滋养层细胞和子宫内膜上皮细胞均表达滋养蛋白,其通过同源性滋养蛋白-滋养蛋白结合介导顶端细胞黏附。我们推测滋养蛋白在胚胎着床中的功能是人类所特有的,并研究了滋养蛋白、味觉蛋白和附睾蛋白在异位妊娠(一种人类特有的情况)中的表达。在输卵管妊娠中,滋养层细胞和输卵管上皮中均发现这三种蛋白的高水平表达。母体细胞中的滋养蛋白表达在与滋养层细胞相邻的区域特别高,而在宫内妊娠或未妊娠女性的完整输卵管中几乎检测不到滋养蛋白。当完整输卵管外植体与人绒毛膜促性腺激素(hCG)一起孵育时,上皮细胞中的滋养蛋白表达增强。由于人类囊胚的滋养外胚层在着床前后都会分泌hCG,这些结果表明来自人类胚胎的hCG诱导母体细胞表达滋养蛋白。由于hCG的β亚基和滋养蛋白基因在哺乳动物中已经分化,本研究表明hCG和滋养蛋白在人类胚胎着床中具有独特作用,包括异位妊娠的发病机制。