Zhang L, Liu X-R, Liu J-Z, Song Y-X, Zhou Z-Q, Cao B-Y
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Reprod Domest Anim. 2017 Dec;52(6):1081-1092. doi: 10.1111/rda.13031. Epub 2017 Jul 30.
Proper HOXA10 expression was essential for endometrial receptivity what was crucial for successful embryo implantation in mammalian. This study confirmed that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR, selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed in the goat endometrium at gestational day 15 (D15) compared with gestational day 5 (D5), suggesting that there were some other factors regulated the expression of HOXA10 during the development of goat endometrium in vivo. What's more, HOXA10 gene silencing (HOXA10-siRNA) resulted in gEECs apoptosis in vitro, and it regulated the protein levels of oestrogen receptor a (ERa), progesterone receptor B (PRb), insulin-like growth factor 1 receptor (IGF1R), BCL-2, pleiotrophin (PTN), AKT and p-JNK in gEECs. Furthermore, HOXA10 might regulate the protein levels of endometrial receptivity biomarker genes, including vascular endothelial growth factor (VEGF), osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in gEECs. In conclusion, miR-182 targeted HOXA10 selectively in EECs in vitro, and HOXA10 played an important role in maintaining the function of EECs in dairy goats.
适当的HOXA10表达对于子宫内膜容受性至关重要，而子宫内膜容受性对于哺乳动物胚胎成功着床至关重要。本研究证实，miR-182通过与HOXA10的3'UTR结合来调节其表达水平，在体外选择性下调山羊子宫内膜上皮细胞（gEECs）而非基质细胞（gESCs）中的HOXA10。然而，与妊娠第5天（D5）相比，妊娠第15天（D15）时山羊子宫内膜中HOXA10和miR-182均上调，这表明在山羊子宫内膜体内发育过程中存在其他一些因素调节HOXA10的表达。此外，HOXA10基因沉默（HOXA10-siRNA）在体外导致gEECs凋亡，并调节gEECs中雌激素受体α（ERα）、孕激素受体B（PRb）、胰岛素样生长因子1受体（IGF1R）、BCL-2、多效生长因子（PTN）、AKT和p-JNK的蛋白水平。此外，HOXA10可能调节gEECs中子宫内膜容受性生物标志物基因的蛋白水平，包括血管内皮生长因子（VEGF）、骨桥蛋白（OPN）、环氧合酶-2（COX-2）和催乳素受体（PRLR）。总之，miR-182在体外EECs中选择性靶向HOXA10，且HOXA10在维持奶山羊EECs功能中发挥重要作用。
