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

Introduction

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).

Need for Effective Treatments

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.

Requirements for Preclinical Models

Preclinical models must:

• Accurately represent the organ-specific tissue.
• Be amenable to high-throughput experimentation with automated analysis.
• 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.

Project Objectives

The applicant will address this gap by:

1. Characterising the relevant properties of human testicular tissue.
2. Establishing their effects on resident cell function.

Development of Hydrogel Material

The resulting data will inform the development of a hydrogel material with properties tailored to match those of the native tissue.

Fabrication and Analysis

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. This will form the first representative, reliable, and reproducible model of the human testes.

Validation and Application

The RE3MODEL system will be validated against established in vitro models and used to:

• Determine the therapeutic mechanisms of current empirical medical strategies.
• Identify and optimise the most promising treatment approaches as an exemplar application.