Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine Northwest A&F University, Yangling 712100, China.
Int J Mol Sci. 2023 Feb 18;24(4):4121. doi: 10.3390/ijms24044121.
MSX1 is an important member of the muscle segment homeobox gene (Msh) family and acts as a transcription factor to regulate tissue plasticity, yet its role in goat endometrium remodeling remains elusive. In this study, an immunohistochemical analysis showed that MSX1 was mainly expressed in the luminal and glandular epithelium of goat uterus, and the MSX1 expression was upregulated in pregnancy at days 15 and 18 compared with pregnancy at day 5. In order to explore its function, goat endometrial epithelial cells (gEECs) were treated with 17 β-estrogen (E), progesterone (P), and/or interferon-tau (IFNτ), which were used to mimic the physiological environment of early pregnancy. The results showed that MSX1 was significantly upregulated with E- and P-alone treatment, or their combined treatment, and IFNτ further enhanced its expression. The spheroid attachment and PGE2/PGF2α ratio were downregulated by the suppression of MSX1. The combination of E, P, and IFNτ treatment induced the plasma membrane transformation (PMT) of gEECs, which mainly showed the upregulation of N-cadherin (CDH2) and concomitant downregulation of the polarity-related genes (, , , , and ). The knockdown of MSX1 partly hindered the PMT induced by E, P, and IFNτ treatment, while the upregulation of CDH2 and the downregulation of the partly polarity-related genes were significantly enhanced when MSX1 was overexpressed. Moreover, MSX1 regulated the CDH2 expression by activating the endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR) pathway. Collectively, these results suggest that MSX1 was involved in the PMT of the gEECs through the ER stress-mediated UPR pathway, which affects endometrial adhesion and secretion function.
MSX1 是肌肉节同源盒基因（Msh）家族的重要成员，作为转录因子调节组织可塑性，但它在山羊子宫内膜重塑中的作用仍不清楚。在这项研究中，免疫组织化学分析表明，MSX1 主要在山羊子宫的腔上皮和腺上皮中表达，与妊娠第 5 天相比，妊娠第 15 天和第 18 天的 MSX1 表达上调。为了探讨其功能，用 17β-雌二醇（E）、孕酮（P）和/或干扰素-τ（IFNτ）处理山羊子宫内膜上皮细胞（gEECs），以模拟早期妊娠的生理环境。结果表明，E 和 P 单独处理或联合处理均显著上调 MSX1 的表达，IFNτ 进一步增强其表达。MSX1 抑制后，球体附着和 PGE2/PGF2α 比值降低。E、P 和 IFNτ 联合处理诱导 gEECs 的质膜转化（PMT），主要表现为 N-钙黏蛋白（CDH2）上调，同时与极性相关基因（,,, 和 ）下调。MSX1 敲低部分阻碍了 E、P 和 IFNτ 处理诱导的 PMT，而当 MSX1 过表达时，CDH2 的上调和部分极性相关基因的下调显著增强。此外，MSX1 通过激活内质网（ER）应激介导的未折叠蛋白反应（UPR）通路调节 CDH2 的表达。总之，这些结果表明，MSX1 通过 ER 应激介导的 UPR 通路参与 gEECs 的 PMT，影响子宫内膜的黏附和分泌功能。
