Afshar Yalda, Stanculescu Adina, Miele Lucio, Fazleabas Asgerally T
Department of Obstetrics and Gynecology, University of Illinois at Chicago, 820 S Wood Street, M/C 808, Chicago, IL 60612-7313, USA.
J Assist Reprod Genet. 2007 Jul;24(7):296-302. doi: 10.1007/s10815-007-9149-2.
Failed implantation is a major limiting factor in infertility and early pregnancy loss. In primates, human chorionic gonadotropin mediated inhibition of stromal cell apoptosis and their subsequent differentiation into decidual cells is critical for successful embryo implantation. A major regulator of cell survival and differentiation is the Notch receptor, which transduces extracellular signals responsible for cell fate determination during development. Proteolytic cleavage of full-length Notch1 releases an active intracellular peptide, which later translocates to the nucleus and activates gene transcription. Induction of Notch1 during the window of uterine receptivity in stromal fibroblasts in response to chorionic gonadotropin upregulates anti- apoptotic genes and induces alpha-smooth muscle actin, enabling stromal cells to proliferate and differentiate into a decidualized phenotype. As such, prior to implantation the embryonic signal, chorionic gonadotropin, rescues stromal fibroblasts from normal regression at the end of each ovarian cycle.
We are suggesting that chorionic gonadotropin and Notch1 coordinately regulate decidualization by preventing apoptosis of endometrial stromal fibroblasts, averting uterine sloughing, and promoting cell survival and differentiation into the decidualized phenotype, which is critical for the maintenance of pregnancy.
种植失败是不孕症和早期妊娠丢失的主要限制因素。在灵长类动物中，人绒毛膜促性腺激素介导的对基质细胞凋亡的抑制及其随后向蜕膜细胞的分化对于胚胎成功着床至关重要。细胞存活和分化的一个主要调节因子是Notch受体，它在发育过程中传导负责细胞命运决定的细胞外信号。全长Notch1的蛋白水解切割会释放出一种活性细胞内肽，该肽随后转运至细胞核并激活基因转录。在子宫接受期窗口期间，对绒毛膜促性腺激素作出反应的基质成纤维细胞中Notch1的诱导会上调抗凋亡基因并诱导α-平滑肌肌动蛋白，使基质细胞增殖并分化为蜕膜化表型。因此，在着床前，胚胎信号绒毛膜促性腺激素可在每个卵巢周期结束时使基质成纤维细胞免于正常退化。
我们认为，绒毛膜促性腺激素和Notch1通过防止子宫内膜基质成纤维细胞凋亡、避免子宫脱落以及促进细胞存活和分化为蜕膜化表型来协调调节蜕膜化，这对于维持妊娠至关重要。
