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The role of chorionic gonadotropin and Notch1 in implantation

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Abstract

Purpose

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 α-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.

Conclusion

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.

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Acknowledgement

This work was supported by NIH HD 42280.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Illinois at Chicago, 820 S Wood Street, M/C 808, Chicago, IL, 60612-7313, USA

    Yalda Afshar & Asgerally T. Fazleabas

  2. Department of Pathology, Cardinal Cancer Center, Loyola University Medical Center, Maywood, IL, USA

    Adina Stanculescu & Lucio Miele

Authors
  1. Yalda Afshar
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  2. Adina Stanculescu
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  3. Lucio Miele
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  4. Asgerally T. Fazleabas
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Correspondence to Asgerally T. Fazleabas.

Additional information

Chorionic gonadotropin and Notch1 inhibit stromal cell apoptosis and induce decidualization in the primate endometrium.

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Afshar, Y., Stanculescu, A., Miele, L. et al. The role of chorionic gonadotropin and Notch1 in implantation. J Assist Reprod Genet 24, 296–302 (2007). https://doi.org/10.1007/s10815-007-9149-2

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