Phenotypic and immuonological characterisation of common fallopian tube pathologies and their impact on fertility

Abstract

The fallopian tubes (FT) play an essential role in human reproduction, serving as the site for fertilisation and initial embryo transport to the uterus. Proper functioning of the FT is critical for fertility, with tubal factor infertility accounting for a significant proportion of infertility cases. Hydrosalpinx is a common tubal dysfunction condition characterised by non-patent, fluid-filled FT and accounts for approximately 30% of tubal-related infertility. This thesis aims to enhance our understanding of FT physiology and pathology through comprehensive phenotypic and immunological characterisation of patient samples and in vitro modelling of tubal damage. The first objective was to explore the potential for tubal decidualisation, a key physiological process that transforms endometrial stromal cells into specialised secretory cells that prepare the uterine environment for embryo implantation. Initially, a systematic review evaluated existing evidence for decidualisation markers in the FT. This was complemented by experimental investigations comparing markers of decidualisation in FT tissue and matched endometrial samples using immunohistochemistry (IHC) and quantitative PCR (qPCR). The results indicate that the FT can exhibit decidual changes under specific hormonal and physiological conditions. However, additional validation of the suitability of employing IHC or alternative techniques for evaluating decidualisation markers requires clarification through better markers and advanced technologies for future research. The second objective investigated the immune cell profile of the FT under both healthy and pathological conditions, specifically hydrosalpinx. A systematic review dissecting the immune cell profiles of the FT in health and benign pathological conditions was followed by IHC characterisation of immune cell populations in healthy and hydrosalpinx-affected tubes and matched endometrial tissue. Findings revealed that hydrosalpinx significantly alters the immune microenvironment of the FT, affecting both innate and adaptive immune responses. Notably, differential expression of immune markers including CD3, CD4, CD45, CD56, and CD68 was also observed in endometrial tissue of those affected by hydrosalpinx. This immunological disruption suggests a pathological spread of inflammation from the FT likely contributes to impaired endometrial receptivity, providing an explanation for subfertility associated with hydrosalpinx. The final aim was to develop a robust and physiologically relevant three- dimensional (3D) in vitro model of the human FT. This model successfully replicates the cellular composition, structure, and functional characteristics of the FT. It provides an effective platform to study tubal pathologies and tubal factor infertility under controlled laboratory conditions. This enabling platform will allow researchers to test new therapeutic interventions and deepen understanding of tubal disease mechanisms. In conclusion, this thesis significantly advances the understanding of the FT’s role in fertility and infertility, particularly regarding hydrosalpinx. This study elucidates the FT’s potential for decidual-like changes, immunological alterations associated with pathology, and develops an advanced 3D model, offering valuable insights and practical tools for clinicians, reproductive biologists, and fertility researchers.