Luo Xi, Yang Renxiang, Bai Yun, Li Lei, Lin Na, Sun Lan, Liu Jianjun, Wu Ze
Faculty of Life science and Technology, Kunming University of Science and Technology, Kunming, China.
Medical School, Kunming University of Science and Technology, Kunming, China.
Ann Transl Med. 2021 Apr;9(8):662. doi: 10.21037/atm-21-596.
Patients with elevated circulating progesterone concentrations on the day of the human chorionic gonadotropin (hCG) trigger had relatively low implantation rates during assisted reproductive treatments. In this study, we assess the hypothesis that different concentrations of progesterone regulate the expression of homeobox protein A10 (HOXA10) and its downstream genes through miRNA-135a.
MicroRNA-135a (), , beta3-integrin (), and empty spiracles homeobox-2 () expression levels in endometrial tissues from patients with elevated progesterone were measured. To determine the threshold of progesterone level which can impair implantation, Ishikawa cells were used to determine the expression of the aforementioned 4 genes after exposure to 5 graded concentrations of progesterone. The dual-luciferase reporter assay was used to verify whether miR-135a regulated the expression of HOXA10. Furthermore, the effects of HOXA10 on the expression of key endometrial receptivity genes and were confirmed.
High progesterone levels promoted miR-135a expression in vivo, and miR-135a bound to the 3'-untranslated region (3'-UTR) of mRNA to inhibit HOXA10 expression. Reduction of HOXA10 promoted EMX2 expression and inhibited ITG-3 production. Progesterone promoted the expression of HOXA10 at low concentrations. However, when the concentration was greater than 10 ng/mL, progesterone inhibited HOXA10 by promoting miR-135a expression, thereby altering the expression of related genes and affecting endometrial receptivity.
, the trend in miR-135a expression (which first decreased and then increased) was in direct contrast to that of expression (which first increased and then decreased) as progesterone levels increased. The key factors regulating endometrial receptivity included ITGβ3 and EMX2, which were confirmed to be regulated by HOXA10. High progesterone levels affected miR-135a expression, and miR-135a inhibited expression, thereby affecting endometrial receptivity.
在人绒毛膜促性腺激素（hCG）触发日循环孕酮浓度升高的患者在辅助生殖治疗期间着床率相对较低。在本研究中，我们评估不同浓度的孕酮通过miRNA - 135a调节同源框蛋白A10（HOXA10）及其下游基因表达的假说。
测量孕酮升高患者子宫内膜组织中微小RNA - 135a（miR - 135a）、整合素β3（ITGβ3）和空泡化盒蛋白2（EMX2）的表达水平。为确定可损害着床的孕酮水平阈值，使用 Ishikawa 细胞在暴露于 5 个梯度浓度的孕酮后测定上述 4 种基因的表达。采用双荧光素酶报告基因测定法验证 miR - 135a 是否调节 HOXA10 的表达。此外，证实了 HOXA10 对关键子宫内膜容受性基因 ITGβ3 和 EMX2 表达的影响。
高孕酮水平在体内促进 miR - 135a 表达，且 miR - 135a 与 HOXA10 mRNA 的 3' - 非翻译区（3' - UTR）结合以抑制 HOXA10 表达。HOXA10 的减少促进 EMX2 表达并抑制 ITGβ3 产生。低浓度孕酮促进 HOXA10 表达。然而，当浓度大于 10 ng/mL 时，孕酮通过促进 miR - 135a 表达抑制 HOXA10，从而改变相关基因的表达并影响子宫内膜容受性。
随着孕酮水平升高，miR - 135a 表达趋势（先降低后升高）与 HOXA10 表达趋势（先升高后降低）直接相反。调节子宫内膜容受性的关键因子包括 ITGβ3 和 EMX2，证实它们受 HOXA10 调节。高孕酮水平影响 miR - 135a 表达，且 miR - 135a 抑制 HOXA10 表达，从而影响子宫内膜容受性。
