Deficiency of PARP-1 and PARP-2 in the mouse uterus results in decidualization failure and pregnancy loss
Andrew M. Kelleher, Rohit Setlem, Françoise Dantzer, Francesco J. DeMayo, John P. Lydon, W. Lee Kraus
Abstract
Significance This study identifies an unknown role for PARP-1 and PARP-2 in mediating pregnancy success. Utilizing a combination of mouse genetic models, pharmacological inhibitors, and histological and transcriptomic analysis, we identified roles for PARPs and ADP ribosylation (ADPRylation) during the establishment and maintenance of pregnancy. We show that the absence of PARP-1 and PARP-2 augments the DNA damage response during early pregnancy, presumably by ADPRylating substrate proteins, culminating in aberrant decidualization and ultimately pregnancy failure. These findings could be leveraged to develop contraceptives or as biomarkers of uterine receptivity and stromal cell decidualization.