The Laboratory of Cell and Developmental Biology, Northeast Agricultural University, Harbin, 150030, China.
Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, 250014, China.
Theriogenology. 2022 Mar 1;180:130-136. doi: 10.1016/j.theriogenology.2021.12.022. Epub 2021 Dec 18.
Ruminants have a superficial implantation pattern. The extended conceptus attaches to the receptive endometrium to form the cotyledonary placenta. During the attachment, a large number of events occur at the maternal-fetal interface. However, the related molecular mechanisms have not been fully understood. Integrin beta8 (ITGB8) is a subunit of integrin beta involved in embryo implantation. In this study, we determined peri-implantation expression and regulation of ITGB8 in goat uterus. The mRNA and protein levels of ITGB8 were both high in goat endometrial luminal epithelium (LE) and superficial glandular epithelium (sGE) during the adhesion period (Days 16-19 of pregnancy). Such expression profile was opposite to that of microRNA-187 (miR-187). Then, we validated that miR-187 targeted the 3' untranslated region (UTR) of ITGB8 in primary goat endometrial epithelial cells (EECs). In EECs, inhibition of miR-187 resulted in not only up-regulated ITGB8 level but also reduced cell proliferation and focal adhesion kinase (FAK) activity. Moreover, ITGB8 and miR-187 were regulated by interferon tau (IFNT). Altogether, in goat, the miR-187/ITGB8 axis may be involved in conceptus attachment and is downstream of IFNT. Our results will help us better understand the mechanisms of ruminant implantation and may provide a useful tool to improve the reproduction ratio for ruminants.
反刍动物的着床模式较为表浅。扩展的胚体附着在接受性子宫内膜上形成绒毛胎盘。在附着过程中，母胎界面会发生大量事件。然而，相关的分子机制尚未完全阐明。整合素β8（ITGB8）是参与胚胎着床的整合素β亚基。在本研究中，我们确定了整合素β8在山羊子宫中的着床前表达和调节。在妊娠第 16-19 天的附着期，山羊子宫内膜腔上皮（LE）和浅层腺上皮（sGE）中 ITGB8 的 mRNA 和蛋白水平均较高。这种表达模式与 microRNA-187（miR-187）相反。然后，我们验证了 miR-187 靶向山羊原代子宫内膜上皮细胞（EEC）中 ITGB8 的 3'非翻译区（UTR）。在 EEC 中，抑制 miR-187 不仅导致 ITGB8 水平上调，还导致细胞增殖和粘着斑激酶（FAK）活性降低。此外，ITGB8 和 miR-187 受干扰素 tau（IFNT）调节。总之，在山羊中，miR-187/ITGB8 轴可能参与胚胎附着，是 IFNT 的下游。我们的研究结果将有助于我们更好地理解反刍动物着床的机制，并可能为提高反刍动物的繁殖率提供有用的工具。
