Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 518, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2020.110946
Keywords
Poly(ADP-Ribose) polymerase-2 (PARP-2); Caspase-8; Endometrial receptivity; Decidualization; Embryo implantation; Delayed implantation; Implantation failure
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Funding
- Indian Council of Medical Research (ICMR), New Delhi [5/10/10/2011-RHN]
- Department of Science and Technology (DST), New Delhi [SR/BO/BB-043/2011, EMR/2016/005278-2018]
- Council of Scientific and Industrial Research (CSIR), New Delhi [21/12/2014(ii) EU-v]
- ICMR, New Delhi [3/1/3/JRF-2011/HRD-75, 61102]
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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.
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