炎性衰老影响子宫内膜容受性的机制研究进展

Progress in the study of the effect of inflammaging on endometrial receptivity

女性年龄是决定生育力的重要因素,随着年龄增长,女性生殖能力逐渐下降。子宫内膜容受性下降是女性年龄相关性生殖功能下降的主要原因之一。机体在衰老过程中,由衰老细胞分泌的一系列促炎因子介导一种慢性、低度、系统性、非可控性的炎症状态,称为炎性衰老。外周循环以及子宫局部的促炎因子例如白细胞介素(IL)-1β、IL-6、白血病抑制因子(LIF)、肿瘤坏死因子α(TNF-α)等的积累,与雌孕激素协同作用,通过调控同源框A10(HOXA10)、整合素αvβ3、黏蛋白1(MUC1)、基质金属蛋白酶(MMPs)等子宫内膜容受性标志性分子的表达和功能,损伤子宫内膜稳态,导致女性年龄相关性子宫内膜容受性下降。本文从子宫内膜容受性的形态学标志胞饮突的生长发育,以及子宫内膜容受性标志分子MMPs、LIF、MUC1、肝素结合性表皮生长因子(HB-EGF)、整合素αvβ3、HOXA10等多个方面对炎性衰老影响子宫内膜容受性的分子机制作一综述。

Female age is one of the most important factors determining fecundity,which gradually declines with natural aging.The decrease of endometrial receptivity is the major cause for age-related decline of fecundity.In the progress of aging,senescent cells secrete inflammatory factors inducing a chronic,low-degree,systemic,uncontrolled inflammatory state,termed“inflammaging”.Accumulated inflammatory mediators such as interleukin-1β(IL-1β),interleukin-6(IL-6),leukaemia inhibitory factor(LIF)and tumor necrosis factor-α(TNF-α)in peripheral circulation and local uterus,together with estrogen and progesterone,lead to the abnormal expression and function of markers of endometrial receptivity such as homeobox A10(HOXA10),integrinαvβ3,mucoprotein(MUC1)and matrix metalloproteinase(MMP).This disturbs the endometrial homeos-tasis and contributes significantly to the age-related decline of endometrial receptivity.In this paper,we reviewed the molecular mechanisms of the effect of inflammaging on endometrial receptivity with the foucus on the development of pinopodes,which is a morphological marker of endometrial receptivity and the involvement of other markers including MMPs,LIF,MUC1,heparin-binding epidermal growth factor(HB-EGF),integrinαvβ3 and HOXA10.