Essential Role of CRIM1 on Endometrial Receptivity in Goat

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.

Autophagy as a Therapeutic Target of Natural Products Enhancing Embryo Implantation

“…They also demonstrated that Atg16L1 is necessary for proper decidualization and blastocyst implantation using mice with a hypomorphic allele of the Atg16L1 gene (causes a partial loss of function) [99]. In addition, cysteine-rich transmembrane BMP regulator 1 (CRIM1) functions as a regulator of endometrial receptivity at least in part by facilitating Atg7-dependent autophagy in the goat endometrium [100].…”

“…Several studies have been conducted on the pharmacological or genetic abrogation of autophagy [98][99][100][101], and the role of autophagy in embryo implantation has been largely elucidated. However, the effects of autophagic activators on embryo implantation are not uniform, although the pathways of autophagy activation by these compounds are similar.…”

The involvement of the primo vascular system in local enteritis and its modification by electroacupuncture

“…After the unique nucleus shape of the PVs was determined, the posterior part of the suspected PVS was taken out for scanning electron microscopy (SEM) analysis. The SEM analysis was performed as reported in a previous study (35). Briefly, after fixation with 2.5% glutaraldehyde in phosphate buffer at 4°C overnight, the suspected PVS samples with rod-shaped nuclei were dehydrated in ethanol, and critical point-dried.…”

Baicalin alleviates endometrial inflammatory injury through regulation of tight junction proteins

“…Virus packaging and cell transfection were performed as previously reported. 12,22 As reported previously, we also generated recombinant lentiviral vectors encoding GFP-LC3-RFP and GFP-LC3, which are fluorescent probes used to evaluate autophagic flux. Goat MAP1LC3B cDNA (GenBank accession number: XM_018061829.1) was used to generate these vectors.…”

“…11 Our previous study demonstrated that autophagy is involved in regulating cell proliferation, cell adhesion, and PG secretion in goat endometrial epithelial cells during early pregnancy. 12 Rizzo et al demonstrated that the downregulation of autophagic flux induced by LPS was counteracted by pretreatment with baicalin in intestinal epithelial cells. 13 Activation of autophagy in brain microvascular endothelial cells maintained the integrity of the blood-brain barrier during early hypoxia-induced cerebrovascular impairment.…”