Multiple roles for heparin-binding epidermal growth factor-like growth factor are suggested by its cell-specific expression during the human endometrial cycle and early placentation.

Multiple roles for heparin-binding epidermal growth factor-like growth factor are suggested by its cell-specific expression during the human endometrial cycle and early placentation.
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DOI:
10.1210/jcem.84.9.5980
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发表时间:
1999-09
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
通讯作者:
R. Leach;Reda Khalifa;N. Ramirez;S. Das;Jue Wang;S. Dey;R. Romero;D. Armant
R. Leach;Reda Khalifa;N. Ramirez;S. Das;Jue Wang;S. Dey;R. Romero;D. Armant
中科院分区:
其他
文献类型:
--
作者:
R. Leach;Reda Khalifa;N. Ramirez;S. Das;Jue Wang;S. Dey;R. Romero;D. Armant

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表皮生长因子(EGF)受体的胚胎表达,以及其配体肝素结合EGF样生长因子(HB-EGF)的胚胎和激素依赖性子宫分泌,与囊胚着床期有时间相关性。我们采用免疫组织化学和原位杂交技术检测了月经周期期间人子宫内膜HB-EGF的时间细胞特异性表达。还检查了妊娠早期植入部位,以确定蜕膜和胎儿组织中的HB-EGF蛋白水平。在子宫内膜基质中,HB-EGF蛋白表达在增殖晚期显著升高,在分泌早期显著降低。而输卵管上皮细胞、腺上皮细胞和血管内皮细胞在月经中期至月经周期第20天积累了该蛋白,并在子宫接受着床期达到表达高峰。HB-EGF的表达在月经周期结束前急剧下降。HB-EGF信使核糖核酸的时空表达表现出类似的模式。妊娠早期,蜕膜、绒毛和绒毛外滋养细胞群中均可见HB-EGF免疫染色。这些发现表明,HB-EGF通过旁分泌和自分泌信号通路促进细胞植入和滋养细胞侵袭,如细胞穿透基质并取代小动脉内皮。
Embryonic expression of the epidermal growth factor (EGF) receptor as well as embryonic and steroid-dependent uterine secretion of its ligand, heparin-binding EGF-like growth factor (HB-EGF), are temporally associated with the period of blastocyst implantation. We examined the temporal cell type-specific expression of HB-EGF in human endometrium during the menstrual cycle by immunohistochemistry and in situ hybridization. Early first trimester implantation sites were also examined to determine HB-EGF protein levels in decidual and fetal tissues. In the endometrial stroma, HB-EGF protein expression increased markedly during the late proliferative phase and then decreased in the early secretory phase. By contrast, luminal and glandular epithelial cells as well as blood vessel endothelium accumulated the protein between midcycle and cycle day 20, with peak expression observed during the period of uterine receptivity for implantation. HB-EGF expression decreased dramatically at the end of the cycle, before menses. Spatiotemporal expression of HB-EGF messenger ribonucleic acid demonstrated a similar pattern. During early pregnancy, HB-EGF immunostaining was noted in the decidua and in both villous and extravillous trophoblast populations. These findings suggest that HB-EGF promotes implantation and trophoblast invasion through paracrine and autocrine signaling as cells penetrate the stroma and displace the arteriole endothelium.