Essential Role of CRIM1 on Endometrial Receptivity in Goat.

Essential Role of CRIM1 on Endometrial Receptivity in Goat.
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DOI:
10.3390/ijms22105323
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发表时间:
2021-05-18
影响因子:
5.6
通讯作者:
Ding Y
Ding Y
中科院分区:
生物学2区
文献类型:
--
作者:
Yang D;Liu A;Zhang Y;Nan S;Yin R;Lei Q;Zhu H;Chen J;Han L;Ding M;Ding Y

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在家养反刍动物中,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关于子宫内膜容受性调节的几种分子,但是由于该性状的复杂性质,关于子宫内膜容受性调节的机制仍然未知。在这项工作中,我们证明了富含半胱氨酸的跨膜骨形态发生蛋白(BMP)调节因子1(CRIM 1)作为一种新的调节因子在体外山羊子宫内膜容受性的调节。我们的研究结果表明,激素和IFN-τ增加山羊子宫内膜上皮细胞(EECs)CRIM 1的表达。通过特异性shRNA敲低CRIM 1阻碍细胞增殖、细胞粘附和前列腺素(PGs)分泌,从而破坏正常的子宫内膜容受性。我们进一步证实,由于CRIM 1干扰的感受性缺陷表型通过在EECs中过表达ATG 7而恢复,而ATG 7的缺失进一步损害了感受性表型。此外,我们的研究结果表明,改变ATG 7的表达影响活性氧(ROS)的产生。此外,mR-143- 5 p被证明是一个潜在的上游因素CRIM 1调节子宫内膜容受性的EECs。综上所述,CRIM 1作为miR-143- 5 p的下游靶点,对ATG 7依赖的自噬、细胞增殖、细胞粘附和PG分泌具有调节作用,为早期妊娠失败的诊断和治疗以及提高人工生殖成功率提供了新的靶点。
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.
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