Essential Role of CRIM1 on Endometrial Receptivity in Goat.

Diqi Yang,Ruiling Yin,Mingxing Ding,Li Han,Yi Ding,Sha Nan,Qianghui Lei,Hongmei Zhu,Ai Liu,Jianguo Chen,Yanyan Zhang

doi:10.3390/ijms22105323

Diqi Yang, Ruiling Yin + Show 9 more

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https://doi.org/10.3390/ijms22105323

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Abstract

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.

Highlights

Published: 18 May 2021In domestic ruminants, early pregnancy failure is one of the main reasons why pregnancy cannot be established, and suboptimal endometrial receptivity is responsible for two-thirds of implantation failures [1,2]
We found that P4, E2 and IFN-τ treatment increased the activation of the autophagy flux of
Immunofluorescence results showed that P4, E2 and IFN-τ drove the nuclear translocation of transcription factor EB (TFEB), and a significant increase of TFEB nuclear expression was found in the P4, E2 and IFNτ group epithelial cells (EECs) (Figure 1C,D)

Summary

Introduction

Early pregnancy failure is one of the main reasons why pregnancy cannot be established, and suboptimal endometrial receptivity is responsible for two-thirds of implantation failures [1,2]. Recent evidence suggests that Homeobox proteins A10 and A11 (HOXA10, HOXA11) are important for endometrial receptivity, since their deletion induces abnormal uterine stromal and glandular function [5,6]. Integrin subunit beta 1 (ITGB1), integrin subunit beta 3 (ITGB3) and integrin subunit beta 5 (ITGB5) are members of integrins, which interact with the extracellular matrix (ECM) to establish endometrial receptivity and embryo implantation [7]. Secreted phosphoprotein 1 (SPP1) is an ECM protein that is localized to the uterine luminal epithelium during implantation in sheep and binds integrin receptors to promote assembly of focal adhesion [8]. These molecules are well recognized as markers of endometrial receptivity [9–11]

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