Secretory phospholipase A2-X (Pla2g10) is a novel progesterone receptor target gene exclusively induced in uterine luminal epithelium for uterine receptivity in mice

BACKGROUND: Aberration of estrogen (E(2)) and/or progesterone (P(4)) signaling pathways affects expression of their target genes, which may lead to failure of embryo implantation and following pregnancy. Although many target genes of progesterone receptors (PRs) have been identified in uterine stroma, only a few PR targets have been reported in the epithelium. Secretory phospholipase A(2)-(PLA(2))-X, a member of the PLA(2) family that releases arachidonic acids for the synthesis of prostaglandins that are important for embryo implantation, is dysregulated in the endometrium of patients suffering from repeated implantation failure. However, it is not clear whether sPLA(2)-X is directly regulated by ovarian steroid hormones for embryo implantation in the uterus. RESULT: P(4) induced the Pla2g10 encoding of secretory PLA(2)-X in the apical region of uterine LE of ovariectomized mice via PR in both time- and dose-dependent manners, whereas E(2) significantly inhibited it. This finding is consistent with the higher expression of Pla2g10 at the diestrus stage, when P(4) is elevated during the estrous cycle, and at P(4)-treated delayed implantation. The level of Pla2g10 on day 4 of pregnancy (day 4) was dramatically decreased on day 5, when PRs are absent in the LE. Luciferase assays of mutagenesis in uterine epithelial cells demonstrated that four putative PR response elements in a Pla2g10 promoter region are transcriptionally active for Pla2g10. Intrauterine delivery of small interfering RNA for Pla2g10 on day 3 significantly reduced the number of implantation sites, reinforcing the critical function(s) of Pla2g10 for uterine receptivity in mice. CONCLUSIONS: Pla2g10 is a novel PR target gene whose expression is exclusively localized in the apical region of the uterine LE for uterine receptivity for embryo implantation in mice.