Progesterone-based intrauterine device use is associated with a thinner apical layer of the human ectocervical epithelium and a lower ZO-1 mRNA expression.
Progesterone-based intrauterine device use is associated with a thinner apical layer of the human ectocervical epithelium and a lower ZO-1 mRNA expression.
复制标题
基于黄体酮的宫内节育器的使用与人类子宫颈上皮顶端层较薄和 ZO-1 mRNA 表达较低有关。
DOI：
10.1095/biolreprod.114.122887
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发表时间：
2015
影响因子：
3.6
通讯作者：
Broliden,Kristina
中科院分区：
文献类型：
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作者：
Tjernlund,Annelie;Carias,AnnM;Andersson,Sonia;Gustafsson-Sanchez,Susanna;Röhl,Maria;Petersson,Pernilla;Introini,Andrea;Hope,ThomasJ;Broliden,Kristina
目前，激素避孕药是否会影响男性对女性的人类免疫缺陷病毒（HIV）传播正在争论之中。在这项研究中，我们调查是否使用炔雌醇为基础的宫内节育器（pIUD）与宫颈鳞状上皮变薄的影响，下调上皮连接蛋白，和/或改变HIV靶细胞分布在人类宫颈。收集使用pIUD的健康绝经前志愿者的宫颈组织活检，并与两个对照组（即使用复方口服避孕药（COCs）或不使用激素避孕药的女性）的活检进行比较。原位染色和图像分析用于测量上皮厚度和组织活检中HIV受体的存在。上皮连接标志物的信使RNA水平通过定量PCR测量。pIUD组女性的上皮厚度与COC组相似，但与无激素避孕药组女性相比明显更薄。较薄的上皮层的pIUD组是特异性的外宫颈的顶端层。此外，与COC组相比，pIUD组上皮内紧密连接标志物ZO-1的表达水平显著较低。在三个研究组中观察到HIV受体和辅助受体CD 4、CCR 5、DC-SIGN和Langerin的表达水平相似。因此，与对照组相比，使用pIUD的妇女显示外宫颈上皮顶端层较薄，ZO-1表达降低。这些数据表明，使用pIUD可能会削弱宫颈上皮细胞对入侵病原体（包括HIV）的屏障。
Currently, whether hormonal contraceptives affect male to female human immunodeficiency virus (HIV) transmission is being debated. In this study, we investigated whether the use of progesterone-based intrauterine devices (pIUDs) is associated with a thinning effect on the ectocervical squamous epithelium, down-regulation of epithelial junction proteins, and/or alteration of HIV target cell distribution in the human ectocervix. Ectocervical tissue biopsies from healthy premenopausal volunteers using pIUDs were collected and compared to biopsies obtained from two control groups, namely women using combined oral contraceptives (COCs) or who do not use hormonal contraceptives. In situ staining and image analysis were used to measure epithelial thickness and the presence of HIV receptors in tissue biopsies. Messenger RNA levels of epithelial junction markers were measured by quantitative PCR. The epithelial thickness displayed by women in the pIUD group was similar to those in the COC group, but significantly thinner as compared to women in the no hormonal contraceptive group. The thinner epithelial layer of the pIUD group was specific to the apical layer of the ectocervix. Furthermore, the pIUD group expressed significantly lower levels of the tight junction marker ZO-1 within the epithelium as compared to the COC group. Similar expression levels of HIV receptors and coreceptors CD4, CCR5, DC-SIGN, and Langerin were observed in the three study groups. Thus, women using pIUD displayed a thinner apical layer of the ectocervical epithelium and reduced ZO-1 expression as compared to control groups. These data suggest that pIUD use may weaken the ectocervical epithelial barrier against invading pathogens, including HIV.