The role of chorionic gonadotropin and Notch1 in implantation.
OBJECTIVE
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.


CONCLUSIONS
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.
Afshar
Yalda
Y
Department of Obstetrics and Gynecology, University of Illinois at Chicago, 820 S Wood Street, M/C 808, Chicago, IL 60612-7313, USA.
Stanculescu
Adina
A
Miele
Lucio
L
Fazleabas
Asgerally T
AT
D017209:Apoptosis; D006063:Chorionic Gonadotropin / Q000502:physiology*; D010064:Embryo Implantation; D004717:Endometrium / Q000166:cytology; D005260:Female; D006801:Humans; D011247:Pregnancy; D051881:Receptor, Notch1 / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology
D006063:Chorionic Gonadotropin; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1