Vaginal/cervical tissue models: endocrine effects and susceptibility to infection

描述(由申请人提供)：性传播感染(STI)是年轻女性发病率和死亡率的主要原因。生殖激素对性传播感染易感性的影响知之甚少。该项目的总体目标是建立人体阴道和宫颈组织的体外器官模型，以研究内分泌对女性生殖道免疫防御和STI感染机制的影响。在女性生殖激素的影响下，将重建三维、高度分化的阴道-宫颈外全厚(VEC-FT)和宫颈内组织模型，以再现代表生殖周期不同阶段的组织。重建的组织模型将通过将基因表达模式与在月经周期特定阶段采集的自然人类阴道和宫颈组织的基因表达模式进行比较来验证。将检查内分泌对先天免疫的影响以及血管内皮细胞和宫颈组织模型对STI引起的微生物感染的敏感性。一旦建立了器官型组织模型中的感染/传播，将确定感染对组织特性以及先天免疫因子、趋化因子和细胞因子表达的影响。最后，将进行抗微生物药物的安全性和有效性测试。

DESCRIPTION (provided by applicant): Sexually transmitted infections (STIs) are a leading cause of morbidity and mortality in young women. Little is known about the effects of reproductive hormones on susceptibility to STIs. The overall goal of this project is to develop in vitro organotypic models of human vaginal and cervical tissues for studies of endocrine effects on female genital tract immune defense and STI infection mechanisms. Three dimensional, highly differentiated vaginal-ectocervical full-thickness (VEC-FT) and endocervical tissue models will be reconstructed under the influence of female reproductive hormones to reproduce tissues representative of the various phases of the reproductive cycle. The reconstructed tissue models will be validated by comparing gene expression patterns with those of native human vaginal and endocervical tissue harvested at defined stages of the menstrual cycle. Endocrine effects on innate immunity and susceptibility of the VEC and endocervical tissue models to STI-causing microbial infections will be examined. Once infection/transmission in the organotypic tissue models is established, the effect of infection on tissue characteristics and the expression of innate immunity factors, chemokines, and cytokines will be determined. Finally, safety and efficacy testing of anti-microbial agents will be performed.