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

描述（由申请人提供）：性传播感染（STI）是年轻女性发病和死亡的主要原因。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开发人体阴道和宫颈组织的体外器官型模型，用于研究内分泌对女性生殖道免疫防御和STI感染机制的影响。将在雌性生殖激素的影响下重建三维、高度分化的阴道-宫颈外全层（VEC-FT）和宫颈内组织模型，以重现代表生殖周期各个阶段的组织。将通过比较基因表达模式与在月经周期的定义阶段收获的天然人阴道和宫颈内组织的基因表达模式来验证重建的组织模型。将检查内分泌对先天免疫的影响以及VEC和宫颈内组织模型对STI引起的微生物感染的易感性。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征和先天免疫因子、趋化因子和细胞因子表达的影响。最后，将进行抗微生物剂的安全性和有效性试验。

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.