Embryo implantation is a highly complex process involving many regulatory factors, including several micro RNAs (miRNAs/miRs). One miRNA present in the stromal cells of normal endometrium is miR-149, which targets poly (ADP-ribose) polymerase 2 (PARP-2), a gene involved in endometrial receptivity for trophoblast implantation. However, the precise role of miR-149 in the endometrial receptivity during blastocyst implantation is still unknown. We studied miR-149-dependent PARP-2 regulation during trophoblast attachment to endometrial epithelial cells. Using FISH, we found that miR-149 is expressed in mouse endometrial epithelial and stromal cells at implantation and inter-implantation sites. Endometrial receptivity for embryo implantation and attachment is inhibited by the upregulation of miR-149 in the endometrium. Our RT-PCR analysis revealed downregulation of miR-149 in the implantation region of the uterus during the receptive stage (Day 5, 0500 h, p.c.) in the mouse. Under in-vitro conditions, miR-149 overexpression in human endometrial epithelial cells (hEECs) abrogated the human trophoblastic cells spheroid and mouse blastocyst attachment. Subsequently, miR-149 also regulates transformed human endometrial stromal cell (T-hESCs) decidualization by downregulating PARP-2 and upregulating caspase-8 proteins. Overexpression of miR-149 in hEECs and downregulated PARP-2 protein expression, reconfirming that PARP-2 is a downstream target of miR-149 in endometrial cells as well. miR-149 is also able to alter the expression of caspase-8, another PARP-2 regulator. In conclusion, our data indicate that miR-149 is one of the regulators of endometrial receptivity and decidualization for trophoblast implantation, and it exerts the effects by acting on the downstream targets PARP-2 and caspase-8.

中文翻译：

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miRNA-149 靶向子宫内膜上皮和基质细胞中的 PARP-2 以调节滋养层附着过程

胚胎植入是一个高度复杂的过程，涉及许多调节因素，包括几种微 RNA (miRNAs/miRs)。存在于正常子宫内膜基质细胞中的一种 miRNA 是 miR-149，它靶向多聚（ADP-核糖）聚合酶 2 (PARP-2)，这是一种与滋养层植入的子宫内膜容受性有关的基因。然而，miR-149 在胚泡植入过程中在子宫内膜容受性中的确切作用仍然未知。我们研究了滋养层附着于子宫内膜上皮细胞期间 miR-149 依赖性 PARP-2 的调节。使用 FISH，我们发现 miR-149 在植入和植入间位点的小鼠子宫内膜上皮和基质细胞中表达。子宫内膜中 miR-149 的上调抑制了子宫内膜对胚胎植入和附着的容受性。我们的 RT-PCR 分析揭示了小鼠接受阶段（第 5 天，0500 小时，pc）子宫植入区域中 miR-149 的下调。在体外条件下，人类子宫内膜上皮细胞 (hEECs) 中的 miR-149 过表达消除了人类滋养层细胞球体和小鼠胚泡的附着。随后，miR-149 还通过下调 PARP-2 和上调 caspase-8 蛋白来调节转化的人子宫内膜基质细胞 (T-hESCs) 蜕膜化。miR-149 在 hEEC 中的过表达和 PARP-2 蛋白表达的下调，再次证实 PARP-2 也是 miR-149 在子宫内膜细胞中的下游靶标。miR-149 还能够改变另一种 PARP-2 调节剂 caspase-8 的表达。综上所述，