Computational Modelling of Sperm Behaviour in a 3D Virtual Oviduct

The processes by which individual sperm cells navigate the length and complexity of the female reproductive tract and then reach and fertilise the oocyte are fascinating. Numerous complex processes potentially influence the movement of spermatozoa within the tract, resulting in a regulated supply of spermatozoa to the oocytes at the site of fertilisation. Despite significant differences between species, breeds and individuals, these processes converge to ensure that an optimal number of high quality spermatozoa reach the oocytes, resulting in successful fertilisation without a significant risk of polyspermy. Computational modelling provides a useful method for combining knowledge about the individual processes in complex systems to help understand the relative significance of each factor. In this thesis, the first agent based computational model of sperm behaviour within the oviductal environment has been created. First, a generic conceptual model of sperm behaviour within the 3D oviduct is presented. Sperm are modelled as individual cells with a set of behavioural rules defining how they interact with their local environment and regulate their internal state. Secondly, a set of 3D models of the mammalian oviduct were constructed. Histology images of the mouse oviduct were obtained and the path that the oviductal tube follows through the tissue was identified using CUDA based image analysis. This was used to determine cross-sectional topology, and measurements from the cross sections were used to generate a set of accurately scaled 3D models of the oviduct. The process of constructing and validating the agent-based computational model of sperm movement and transport within the oviductal environment is described. The model is grounded in reality, with accurate space and time scales used throughout, and parameters and mechanisms from literature where available. Sensitivity analysis is performed on all parameters, and those which are most sensitive to variation have been identified. The model has been validated against literature were possible, and the limitations of the model, validation and assumptions made are clearly stated. The model has been used to investigate the significance of the oviductal environment on the regulation of sperm distribution and progression to the site of fertilisation, and how changes to that environment alter the distribution. Finally, the potential use for the model and how more complex mechanisms could be integrated in the future are discussed.