Insights into Human Oviduct Physiology and Inflammatory Stimuli Using In Vitro Organoids

Abstract

The human oviduct is a crucial organ of the female reproductive tract that plays a key role in the early reproductive events. It includes four distinct segments and each segment contributes uniquely in the function of the oviduct. The epithelial lining of the oviduct is of key importance for human reproduction as it regulates the tubal environment, including epithelial-sperm interaction. In addition, the luminal fluid of the oviduct provides an optimum microenvironment for embryo development. It contains molecules that contribute to support gamete viability and preimplantation development. Chlamydia trachomatis is a bacterium that causes chlamydial infection and one of the most common causes of sexually transmitted disease worldwide. This asymptomatic bacterial infection may remain undiagnosed or untreated, which in turn ascend to the upper female reproductive tract and infect the oviduct. Infection of the oviduct can result in scarring and damaging inflammation within the microenvironment of the oviduct. The release of pro-inflammatory cytokines during Chlamydial infection may lead to functional damage of the oviduct. Despite the importance of the oviduct, detail on how oviduct responds to the release of pro-inflammatory cytokines during infections is not well known.

This project has used in vitro oviduct organoids to assess whether organoids could be engineered to allow the investigation of sperm-oviduct interaction and investigates the impact of inflammatory mediators on the epithelial cells and luminal fluid of the oviduct. The project has explored the genomic and physiological responses of oviduct organoids. The data showed that the in vitro organoid model clearly recapitulates the in vivo oviduct tissue by expressing the key cellular structures. A complete inversion of the oviduct organoids is achievable for future research on gamete-oviduct interaction. IFNγ is an effective inflammatory mediator and has a significant impact on the epithelial cells of the oviduct. The downregulation of ANXA5 might play a key role in infertility in patients with Chlamydial infection. Oviduct organoids provide a promising platform and a powerful tool for future investigations and to address questions regarding reproductive system.