Ovariectomized mice and postmenopausal women exhibit analogous loss of genital epithelial integrity.
Ovariectomized mice and postmenopausal women exhibit analogous loss of genital epithelial integrity.
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卵巢切除小鼠和绝经后妇女表现出类似的生殖器上皮完整性丧失。
DOI：
10.1080/21688370.2020.1865760
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发表时间：
2021
期刊：
影响因子：
3.1
通讯作者：
Cherpes,ThomasL
中科院分区：
文献类型：
--
作者：
QuispeCalla,NirkE;VicettiMiguel,RodolfoD;Aceves,KristenM;Huang,Huijie;Howitt,Brooke;Cherpes,ThomasL
大约一半的绝经后妇女受到绝经期泌尿生殖综合征（GSM）的影响。GSM的症状，包括阴道刺激和性交困难，发生在雌激素（E）产生减少导致弹性丧失和生殖道组织的其他变化时。虽然注射避孕药醋酸甲羟孕酮（DMPA）的使用同样降低了育龄妇女的血清E浓度，并与生殖器细胞间粘附分子桥粒芯糖蛋白-1（DSG 1）和桥粒芯胶蛋白-1（DSC 1）水平降低以及生殖器上皮屏障功能受损有关，但这些发现与绝经期妇女的相关性尚不确定。本文探索绝经对生殖器上皮完整性的影响，我们检测到绝经和绝经后与绝经前妇女相比，子宫颈外组织中DSG 1和DSC 1的水平显著降低。使用卵巢切除（OVX）小鼠作为绝经模型，我们观察到OVX小鼠阴道组织中DSG 1和DSC 1水平显著低于发情期小鼠。与发情期小鼠和E处理的OVX小鼠相比，DMPA处理的卵巢完整小鼠和OVX小鼠也表现出明显降低的生殖器上皮屏障功能，对生殖器单纯疱疹病毒2型感染的易感性更高，生殖器沙眼衣原体感染的清除延迟。因此，目前的研究确定了类似的损失，生殖器上皮完整性OVX小鼠和绝经和绝经后妇女。通过显示生殖器上皮完整性的丧失与小鼠对细菌和病毒病原体的易感性增加有关，我们的研究结果还优先考虑解决绝经后妇女生殖器上皮完整性降低是否是生殖器感染的重要风险因素。
Roughly half of all postmenopausal women are affected by the genitourinary syndrome of menopause (GSM). Symptoms of GSM, including vaginal irritation and dyspareunia, occur as reduced estrogen (E) production elicits loss of elasticity and other changes in genital tract tissue. While the use of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) likewise lowers serum E concentrations in reproductive age women and is associated with decreased genital levels of the cell-cell adhesion molecules desmoglein-1 (DSG1) and desmocollin-1 (DSC1) and impaired genital epithelial barrier function, the relevance of these findings to women in menopause is uncertain. Exploring the impact of menopause on genital epithelial integrity herein, we detected significantly lower levels of DSG1 and DSC1 in ectocervical tissue from menopausal and postmenopausal vs premenopausal women. Using ovariectomized (OVX) mice as a menopause model, we comparably saw significantly lower vaginal tissue levels of DSG1 and DSC1 in OVX mice vs. mice in estrus. Compared to estrus-stage mice and E-treated OVX mice, DMPA-treated ovary-intact mice and OVX mice also exhibited significantly reduced genital epithelial barrier function, greater susceptibility to genital herpes simplex virus type 2 infection, and delayed clearance of genitalChlamydia trachomatisinfection. Current studies thus identify analogous loss of genital epithelial integrity in OVX mice and menopausal and postmenopausal women. By showing that loss of genital epithelial integrity is associated with increased mouse susceptibility to bacterial and viral pathogens, our findings also prioritize the need to resolve if reduced genital epithelial integrity in postmenopausal women is a significant risk factor for genital infection.