Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Int J Mol Sci. 2021 May 18;22(10):5323. doi: 10.3390/ijms22105323.
In domestic ruminants, endometrial receptivity is related to successful pregnancy and economic efficiency. Despite several molecules having been reported in the past regarding endometrial receptivity regulation, much regarding the mechanism of endometrial receptivity regulation remains unknown due to the complex nature of the trait. In this work, we demonstrated that the cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1 (CRIM1) served as a novel regulator in the regulation of goat endometrial receptivity in vitro. Our results showed that hormones and IFN-τ increased the expression of CRIM1 in goat endometrial epithelial cells (EECs). Knockdown of CRIM1 via specific shRNA hindered cell proliferation, cell adhesion and prostaglandins (PGs) secretion and thus derailed normal endometrial receptivity. We further confirmed that receptivity defect phenotypes due to CRIM1 interference were restored by ATG7 overexpression in EECs while a loss of ATG7 further impaired receptivity phenotypes. Moreover, our results showed that changing the expression of ATG7 affected the reactive oxygen species (ROS) production. Moreover, mR-143-5p was shown to be a potential upstream factor of CRIM1-regulated endometrial receptivity in EECs. Overall, these results suggest that CRIM1, as the downstream target of miR-143-5p, has effects on ATG7-dependent autophagy, regulating cell proliferation, cell adhesion and PG secretion, and provides a new target for the diagnosis and treatment of early pregnancy failure and for improving the success rates of artificial reproduction.
在国内反刍动物中,子宫内膜容受性与妊娠成功和经济效益有关。尽管过去已经报道了几种与子宫内膜容受性调节相关的分子,但由于该特征的复杂性,许多关于子宫内膜容受性调节机制的知识仍然未知。在这项工作中,我们证明富含半胱氨酸的跨膜骨形态发生蛋白(BMP)调节剂 1(CRIM1)在山羊体外子宫内膜容受性调节中作为一种新的调节剂。我们的研究结果表明,激素和 IFN-τ 增加了山羊子宫内膜上皮细胞(EEC)中 CRIM1 的表达。通过特异性 shRNA 敲低 CRIM1 会阻碍细胞增殖、细胞黏附和前列腺素(PG)的分泌,从而扰乱正常的子宫内膜容受性。我们进一步证实,CRIM1 干扰导致的容受性缺陷表型在 EEC 中转染 ATG7 后得到恢复,而 ATG7 的缺失进一步损害了容受性表型。此外,我们的研究结果表明,改变 ATG7 的表达会影响活性氧(ROS)的产生。此外,mR-143-5p 被证明是 EECs 中 CRIM1 调节子宫内膜容受性的潜在上游因子。总的来说,这些结果表明,CRIM1 作为 miR-143-5p 的下游靶标,对 ATG7 依赖性自噬有影响,调节细胞增殖、细胞黏附和 PG 分泌,并为早期妊娠失败的诊断和治疗以及提高人工繁殖成功率提供了一个新的靶点。