Qin L, Wang Y L, Bai S X, Xiao Z J, Herva R, Piao Y S
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China.
Reproduction. 2003 Sep;126(3):383-91. doi: 10.1530/rep.0.1260383.
Investigation of the expression pattern of integrins and their extracellular matrix (ECM) ligands in trophoblasts at the maternal-fetal interface during tubal pregnancy may aid better understanding of the adhesion and invasion of acceptable maternal endometrium by trophoblast cells at the very early stage of human gestation. In this study, spatial and temporal alterations of integrins and ECM ligands were examined in specimens of tubal pregnancies during weeks 3-9 of gestation. In situ hybridization and immunohistochemistry revealed that relatively high levels of integrin alpha(1), beta(1), alpha(5) subunits and heterdimer alpha(5)beta(1) as well as ECM ligands, were displayed in trophoblast cells as early as weeks 3-4 of gestation. Expression peaked during weeks 5-7 and then, with the exception of integrin alpha(1), which remained high, declined slightly up to weeks 8-9 of gestation. Immunoreactive fibronectin, laminin and type IV collagen were detected in column cytotrophoblastic cells (CTB) and some invasive extravillous cytotrophoblast (EVCT) cells and the alterations were coincident with those of the corresponding integrin receptors in EVCT cells. Laminin was strongly stained in EVCT cells that had invaded maternal blood vessels and deep into the interstitium. Maternal epithelial, endothelial and stromal cells also expressed these integrins and ECM ligands. The results indicate their involvement in mediating the adhesion of trophoblasts to the epithelium of the maternal Fallopian tube. The upregulated expression of these molecules in column CTB and invasive EVCT cells may also facilitate the invasion of trophoblasts into the maternal interstitium. Moreover, trophoblasts possessed the potential for self-controlled adhesion and invasion and appear to reach peak invasive capability in the second month of tubal implantation.
研究输卵管妊娠期间母胎界面滋养层细胞中整合素及其细胞外基质(ECM)配体的表达模式,可能有助于更好地理解人类妊娠早期滋养层细胞对母体子宫内膜的粘附和侵袭。在本研究中,对妊娠3-9周输卵管妊娠标本中整合素和ECM配体的时空变化进行了检测。原位杂交和免疫组织化学显示,早在妊娠3-4周时,滋养层细胞中整合素α(1)、β(1)、α(5)亚基和异二聚体α(5)β(1)以及ECM配体就呈现相对较高的水平。表达在5-7周达到峰值,然后,除整合素α(1)仍保持高水平外,直至妊娠8-9周略有下降。在柱状细胞滋养层细胞(CTB)和一些侵袭性绒毛外细胞滋养层(EVCT)细胞中检测到免疫反应性纤连蛋白、层粘连蛋白和IV型胶原,其变化与EVCT细胞中相应整合素受体的变化一致。层粘连蛋白在已侵入母体血管并深入间质的EVCT细胞中强烈染色。母体上皮细胞、内皮细胞和基质细胞也表达这些整合素和ECM配体。结果表明它们参与介导滋养层细胞与母体输卵管上皮的粘附。这些分子在柱状CTB和侵袭性EVCT细胞中的上调表达也可能促进滋养层细胞侵入母体间质。此外,滋养层细胞具有自我控制粘附和侵袭的潜力,并且在输卵管着床的第二个月似乎达到侵袭能力的峰值。