Genital epithelial barrier function is conserved by intravaginal rings releasing etonogestrel and ethinyl estradiol.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Tissue Barriers Pub Date : 2024-01-02 Epub Date: 2023-03-10 DOI:10.1080/21688370.2023.2186672
Mohan Liu, Rodolfo D Vicetti Miguel, Nirk E Quispe Calla, Kristen M Aceves, Linda Fritts, Christopher J Miller, John A Moss, Marc M Baum, Thomas L Cherpes
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引用次数: 0

Abstract

The injectable progestin depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in sub-Saharan Africa although mouse models indicate it weakens genital epithelial integrity and barrier function and increases susceptibility to genital infection. The intravaginal ring NuvaRing® is another contraceptive option that like DMPA suppresses hypothalamic pituitary ovarian (HPO) axis function with local release of progestin (etonogestrel) and estrogen (ethinyl estradiol). As we previously reported that treating mice with DMPA and estrogen averts the loss of genital epithelial integrity and barrier function induced by DMPA alone, in the current investigation we compared genital levels of the cell-cell adhesion molecule desmoglein-1 (DSG1) and genital epithelial permeability in rhesus macaques (RM) treated with DMPA or a NuvaRing®re-sized for RM (N-IVR). While these studies demonstrated comparable inhibition of the HPO axis with DMPA or N-IVR, DMPA induced significantly lower genital DSG1 levels and greater tissue permeability to intravaginally administered low molecular mass molecules. By identifying greater compromise of genital epithelial integrity and barrier function in RM administered DMPA vs. N-IVR, our results add to the growing body of evidence that indicate DMPA weakens a fundamental mechanism of anti-pathogen host defense in the female genital tract.

释放依托孕烯和炔雌醇的阴道环可保持生殖器上皮屏障功能。
注射用孕激素醋酸甲羟孕酮(DMPA)是撒哈拉以南非洲常用的避孕药物,但小鼠模型显示它会削弱生殖器上皮的完整性和屏障功能,并增加生殖器感染的易感性。阴道内环 NuvaRing® 是另一种避孕选择,它与 DMPA 一样,通过局部释放孕激素(依托孕烯)和雌激素(炔雌醇)来抑制下丘脑垂体卵巢轴(HPO)功能。由于我们以前曾报道过用 DMPA 和雌激素治疗小鼠可避免单用 DMPA 引起的生殖器上皮完整性和屏障功能的丧失,因此在目前的调查中,我们比较了用 DMPA 或 NuvaRing®re-sized for RM(N-IVR)治疗的恒河猴(RM)生殖器中细胞-细胞粘附分子 desmoglein-1 (DSG1) 的水平和生殖器上皮的通透性。这些研究表明,DMPA 或 N-IVR 对 HPO 轴的抑制作用相当,但 DMPA 诱导的生殖器 DSG1 水平明显较低,组织对阴道内给药的低分子质量分子的通透性更高。我们的研究结果表明,与N-IVR相比,DMPA对RM生殖器上皮的完整性和屏障功能造成了更大的损害,这为越来越多的证据表明DMPA削弱了女性生殖道抗病原体宿主防御的基本机制增添了新的证据。
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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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