Poly(ADP-ribose) polymerase-2 is essential for endometrial receptivity and blastocyst implantation, and regulated by caspase-8

Mol Cell Endocrinol. 2020 Dec 1:518:110946. doi: 10.1016/j.mce.2020.110946. Epub 2020 Jul 15.

Abstract

Embryo implantation is a very complex process and several factors play important roles. Using a mouse model, we investigated the functions of PARP-2 and caspase-8 during endometrial receptivity for blastocyst implantation. We found that PARP-2 was upregulated at the receptive stage's implantation region and predominantly expressed in the endometrial stromal region, but downregulated during pregnancy failure and pseudopregnancy. To reinforce the necessity of PARP-2 for embryo implantation, we pharmacologically inhibited PARP-2 'before' & 'after' embryo arrival and observed a reduction in blastocyst implantation. Conversely, elevated caspase-8 expression and activity during pseudopregnancy, delayed implantation, and embryo implantation failure conditions and decreased levels in the decidualization exhibited an inverse pattern with PARP-2, suggesting caspase-8 as a negative regulator for embryo implantation. In vitro caspase-8 downregulates the PARP-2 activity in the mouse endometrial epithelial and stromal cells. These data suggest that PARP-2 and its negative regulation by caspase-8 constitute a crucial step in embryo implantation.

Keywords: Caspase-8; Decidualization; Delayed implantation; Embryo implantation; Endometrial receptivity; Implantation failure; Poly(ADP-Ribose) polymerase-2 (PARP-2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 8 / metabolism*
  • Cells, Cultured
  • Down-Regulation
  • Embryo Implantation / genetics*
  • Embryo, Mammalian
  • Endometrium / metabolism
  • Endometrium / physiology*
  • Female
  • Male
  • Mice
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Poly(ADP-ribose) Polymerases / physiology*
  • Pregnancy
  • Protein Processing, Post-Translational

Substances

  • Poly(ADP-ribose) Polymerases
  • Parp2 protein, mouse
  • Caspase 8