Aberration of estrogen (E2) and/or progesterone (P4) 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 A2-(PLA2)-X, a member of the PLA2 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 sPLA2-X is directly regulated by ovarian steroid hormones for embryo implantation in the uterus. P4 induced the Pla2g10 encoding of secretory PLA2-X in the apical region of uterine LE of ovariectomized mice via PR in both time- and dose-dependent manners, whereas E2 significantly inhibited it. This finding is consistent with the higher expression of Pla2g10 at the diestrus stage, when P4 is elevated during the estrous cycle, and at P4-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. 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.

中文翻译：

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分泌型磷脂酶A2-X（Pla2g10）是一种新的孕激素受体靶基因，在子宫腔上皮中专门诱导小鼠的子宫接受性。

雌激素（E2）和/或孕激素（P4）信号通路的异常会影响其靶基因的表达，这可能导致胚胎植入失败和怀孕。尽管在子宫基质中已鉴定出许多孕激素受体（PRs）的靶基因，但在上皮中仅报道了少数PR靶标。分泌型磷脂酶A2-（PLA2）-X是PLA2家族的成员，它释放花生四烯酸，以合成对胚胎着床很重要的前列腺素，但在反复着床失败的患者子宫内膜中却失调。然而，尚不清楚sPLA2-X是否受卵巢类固醇激素直接调节以用于子宫内胚胎植入。P4以时间和剂量依赖性方式通过PR诱导卵巢切除的小鼠子宫LE顶端区域分泌性PLA2-X的Pla2g10编码，而E2显着抑制它。这个发现与在发情周期中P4升高和P4处理的延迟植入时在发情阶段Pla2g10的较高表达是一致的。妊娠第4天（第4天）的血浆中Pla2g10的水平在第5天急剧下降，此时LE中不存在PR。子宫上皮细胞诱变的荧光素酶分析表明，Pla2g10启动子区域中的四个假定的PR反应元件对Pla2g10具有转录活性。在第3天宫腔内递送Pla2g10的小干扰RNA显着减少了植入位点的数量，增强Pla2g10对小鼠子宫接受性的关键功能。Pla2g10是一种新颖的PR靶基因，其表达专门定位在子宫LE的顶端区域，以实现小鼠胚胎植入的子宫接受性。