Sperm induced signalling events in the cells of the female reproductive tract

Richards, James (2023). Sperm induced signalling events in the cells of the female reproductive tract. University of Birmingham. Ph.D.

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Abstract

Female reproductive tract regulation of the function of spermatozoa is relatively well characterised, but little is known about the influence which human sperm cells may have upon the cells of the female reproductive tract. Animal models suggest that signalling factors from the male ejaculate can prime the maternal immune response tolerance of the semi-allogeneic conceptus and elicit alterations in gene expression and the secretory proteome of the oviduct. The purpose of this study was to utilise Ca\(^{2+}\) imaging to identify signalling events that occur in response to factors from the male ejaculate in female reproductive tract cells. Cell line models of granulosa cells, endometrial epithelial cells and oviductal epithelial cells were utilised to establish that oviductal epithelial cells are significantly responsive to a range of semen sample preparations.

A novel series of semen preparation pathways were developed to identify the source of the signalling factor within the male ejaculate. These preparations revealed that the factor was likely to be a protein or peptide derived from the seminal plasma that loosely associated with the surface of spermatozoa and was transported into the upper regions of the female reproductive tract by motile sperm cells where it could elicit [Ca\(^{2+}\)]i oscillations in the oviductal epithelial cells via the release of intracellular Ca\(^{2+}\) stores through mechanisms independent of toll-like receptor 4 activation. Proteomic analysis of sperm conditioned media containing the signalling factor was undertaken and candidate peptides from semenogelin-1 and semenogelin-2 were synthesised, however, these peptides failed to elicit Ca\(^{2+}\) signalling. Further investigation is therefore necessary to elucidate the identity of the signalling factor.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):