Representative, Reliable and Reproducible in vitro Models of the Human Testes

Ziel

Western society is on the brink of a fertility crisis, whereby human sperm counts have dropped by 59% over the past four decades and are projected to reach zero by 2045. Treatments for the primary causes of male infertility have no scientific basis, with urologists relying on ineffective empirical medical strategies (guess work). Identifying effective male fertility treatments requires appropriate preclinical models of the sperm-producing testes that can establish a mechanistic basis for treatment choice, dosage and duration. Preclinical models must accurately represent the organ-specific tissue and be amenable to high-throughput experimentation with automated analysis to ensure that they provide representative, reliable and reproducible data. However, current models necessitate manual low-throughput methods and do not accurately represent testicular tissue as the pertinent tissue properties are unknown. The urological field therefore lacks an appropriate model of the testes upon which to evaluate male infertility treatments.

The applicant will address this gap by characterising the relevant properties of human testicular tissue, and establishing their effects on resident cell function. The resulting data will inform the development of a hydrogel material with properties tailored to match those of the native tissue. Microspheres of the representative hydrogel, containing primary testicular cells arranged to mimic the native tissue structure, will be fabricated using a high-throughput platform and analysed using an automated Raman spectroscope, thereby forming the first representative, reliable and reproducible model of the human testes. The RE3MODEL system will be validated against established in vitro models and used to determine the therapeutic mechanisms of current empirical medical strategies, while also identifying and optimising the most promising treatment approaches as an exemplar application.