Deficiency of PARP-1 and PARP-2 in the mouse uterus results in decidualization failure and pregnancy loss.
Proc Natl Acad Sci U S A
; 118(40)2021 10 05.
Article
em En
| MEDLINE
| ID: mdl-34580230
ABSTRACT
Miscarriage is a common complication of pregnancy for which there are few clinical interventions. Deficiency in endometrial stromal cell decidualization is considered a major contributing factor to pregnancy loss; however, our understanding of the underlying mechanisms of decidual deficiency are incomplete. ADP ribosylation by PARP-1 and PARP-2 has been linked to physiological processes essential to successful pregnancy outcomes. Here, we report that the catalytic inhibition or genetic ablation of PARP-1 and PARP-2 in the uterus lead to pregnancy loss in mice. Notably, the absence of PARP-1 and PARP-2 resulted in increased p53 signaling and an increased population of senescent decidual cells. Molecular and histological analysis revealed that embryo attachment and the removal of the luminal epithelium are not altered in uterine Parp1, Parp2 knockout mice, but subsequent decidualization failure results in pregnancy loss. These findings provide evidence for a previously unknown function of PARP-1 and PARP-2 in mediating decidualization for successful pregnancy establishment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Útero
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Aborto Espontâneo
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Poli(ADP-Ribose) Polimerases
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Decídua
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Poli(ADP-Ribose) Polimerase-1
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article