Temporal and spatial expression of integrins and their extracellular matrix ligands at the maternal-fetal interface in the rhesus monkey during pregnancy

Temporal and spatial expression of integrins and their extracellular matrix ligands at the maternal-fetal interface in the rhesus monkey during pregnancy
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DOI:
10.1095/biolreprod.103.015198
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发表时间:
2003-08-01
影响因子:
3.6
通讯作者:
Piao, YS
Piao, YS
中科院分区:
生物学2区
文献类型:
--
作者:
Qin, L;Wang, YL;Piao, YS

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整合素和细胞外基质蛋白(ECM)介导的滋养层对母体子宫内膜的粘附和侵袭是妊娠复杂生理过程中的关键事件。尽管这一过程主要在小鼠身上得到表征,但灵长类动物的相关机制仍不清楚。我们研究了妊娠第15、25、50和100天以及足月时母胎界面处整合素亚基(α(1)、α(5)、α(6)、β(1)和β(4))及其ECM配体(例如层粘连蛋白(LN)、IV型胶原(Col IV)和纤连蛋白(FN))的表达模式和动态变化。 20只怀孕的恒河猴。免疫组化和原位杂交显示,妊娠第15天滋养层细胞中整合素表达相对较高,并在第25天达到峰值。从第50天到足月表达水平下降。沿着侵袭途径,整合素α(1)、α(5)和β(1)亚基的表达水平从近端到远端逐渐升高,在滋养层壳中达到峰值水平,但在与蜕膜接触的侵袭性绒毛外细胞滋养层(EVCT)细胞中表达水平降低。整合素α(1)、α(5)、β(1)和β(4)亚基在蜕膜基质细胞中也高表达,在母体上皮和内皮细胞中中等表达。免疫反应性FN、LN和Col IV分布于EVCT和蜕膜基质细胞以及部分子宫上皮和内皮细胞中。这些数据表明,母胎界面整合素及其ECM配体的相关表达可能参与妊娠早期滋养层细胞增殖和分化的调节以及滋养层细胞的侵袭加速和侵袭抑制过程的平衡。
The integrin and extracellular matrix protein (ECM)-mediated adhesion and invasion of the receptive maternal uterine endometrium by trophoblasts is a critical event in the complex physiological process of pregnancy. Although the process has been largely characterized in mice, the relevant mechanism in primates remains unclear. We investigated the expression patterns and dynamic alterations of integrin subunits (alpha(1), alpha(5), alpha(6), beta(1), and beta(4)) and their ECM ligands, such as laminin (LN), type IV collagen (Col IV), and fibronectin (FN), at the maternal-fetal interface during Gestational Days 15, 25, 50, and 100 and at full term in 20 pregnant rhesus monkeys. Immunohistochemistry and in situ hybridization revealed that a relatively high expression of integrins occurred in trophoblast cells at Gestational Day 15, with the peak level occurring at Day 25. The expression level decreased from Day 50 to term. Along the invasive pathway, expression levels of integrin alpha(1), alpha(5), and beta(1) subunits were gradually elevated from the proximal to distal column, reaching peak level in the trophoblast shell, but were reduced in those invasive extravillous cytotrophoblast (EVCT) cells in contact with the decidua. Integrin alpha(1),, alpha(5), beta(1), and beta(4) subunits were also highly expressed in decidual stromal cells and moderately expressed in the maternal epithelium and endothelium. Immunoreactive FN, LN, and Col IV were distributed in EVCT and decidual stromal cells and part of the uterine epithelial and endothelial cells. These data suggest that the correlated expression of integrins and their ECM ligands at the maternal-fetal interface might be involved in regulation of cell proliferation and differentiation and the counterbalanced invasion-accelerating and invasion-restraining processes in trophoblast cells during the early stage of pregnancy.