Modelling sperm dispersion within and guidance by microarchitecture

在自然生育中，数千万至数亿个自主运动的精子细胞面临着在女性生殖道复杂微环境中迁移的任务。通常只有数十或数百个细胞到达受精部位，通常最多一个精子会使卵子受精。尽管进行了数十年的研究，但缺乏对这一过程的定量和基于物理的理解;特别是不知道细胞的初始浓度和运动性如何影响受孕的可能性，微结构（褶皱，高粘度流体，纤毛和蠕动电流）影响分散的程度，或者如何将其作为生育治疗或避孕的一部分进行调节。该项目的动机是由微流体实验提供的机会，使女性道的功能，例如墙壁和凹槽，以及流体的流变性，以受控的方式进行实验评估。伯明翰妇女医院人类生殖科学中心已经提供了初步数据，证明壁和略微升高的粘度都可以大大增加精子运输。该项目涉及的数学和计算方法将包括偏微分方程（例如建立在Goldstein-Kac电报方程上），基于个人的模型和贝叶斯参数估计。最终目的是揭示精子活力和浓度、流体性质、流动和微结构影响受孕可能性的机制关系，为男性不育症的诊断提供重要信息，并使女性患者能够避免体外受精等更具侵入性的治疗。

In natural fertility, a population of tens to hundreds of millions of self-motile sperm cells is faced with the task of migrating through the complex microenvironment of the female reproductive tract. Usually only tens or hundreds of cells reach the site of fertilisation, and usually at most one sperm will fertilise the egg. A quantitative and physically-based understanding of this process is lacking, despite decades of research; in particular it is not known how the initial concentration and motility of cells affects the likelihood of conception, the extent to which the microarchitecture (folds, high viscosity fluid, cilia- and peristaltic- currents) influence dispersion, or how this could be modulated as part of fertility treatment or contraception. This project is motivated by the opportunity provided by microfluidic experiments, which enable features of the female tract, for example walls and grooves, and the rheology of the fluid, to be assessed experimentally in a controlled way. Preliminary data are already available from Centre for Human Reproductive Science, Birmingham Women's Hospital, evidencing that both walls and slightly raised viscosity can substantially increase sperm transport. The mathematical and computational methods involved in the project will include partial differential equations (building on for example the Goldstein-Kac telegraph equation), individual-based models, and Bayesian parameter estimation. The ultimate aim will be to uncover the mechanistic relationships through which sperm motility and concentration, fluid properties, flow and microarchitecture influence the likelihood of conception, providing vital information in diagnostics for male infertility, and enabling female patients to avoid more invasive treatments such as in vitro fertilisation.