Periodic Reporting for period 1 - RE3MODEL (Representative, Reliable and Reproducible in vitro Models of the Human Testes)
Période du rapport: 2022-09-01 au 2025-02-28
Previous research has confirmed that human sperm concentrations have dropped considerably over the past 40 years and are projected to drop below the fertility threshold by 2045. Despite this approaching crisis, doctors have no effective treatment for the most common forms of male infertility and current platforms for developing new treatments do not accurately represent the testis' primary function; which is to produce mature sperm. This project will develop a preclinical model that is anticipated to accurately replicate human testicular function and is intended to identify effective treatments for male infertility.
To achieve this task, the researchers coordinating this project will:
(i) Characterise the properties of human testicular tissue so that we understand the tissue that we are trying to represent;
(ii) Develop materials that accurately represent the properties exhibited by testicular tissue;
(iii) Develop systems to fabricate miniature preclinical models at high-throughput;
(iv) Evaluate new treatment strategies using the representative preclinical model.
To achieve this task, the researchers coordinating this project will:
(i) Characterise the properties of human testicular tissue so that we understand the tissue that we are trying to represent;
(ii) Develop materials that accurately represent the properties exhibited by testicular tissue;
(iii) Develop systems to fabricate miniature preclinical models at high-throughput;
(iv) Evaluate new treatment strategies using the representative preclinical model.
To date, this project has:
(i) Characterised the properties of human testicular tissue samples from a diverse patient cohort. This patient cohort includes patients undergoing gender affirming surgery and surgical sperm retrieval. The mechanical properties, protein composition, RNA expression, and spatial protein expression (high-plex) have been comprehensively characterised. Analysis of the resulting datasets will continue until Q3 of 2025 and the resulting dataset will inform the development of representative models;
(ii) Developed materials that accurately represent the properties of testicular tissue. The material can be molded and printed into geometries that mimic the native geometries exhibited by human testicular tissue. Material characterisation and refinement will continue until Q4 of 2025;
(iii) Developed a system for fabricating miniaturised models of the testis at high-throughput. System refinement will continue until Q4 of 2026.
(i) Characterised the properties of human testicular tissue samples from a diverse patient cohort. This patient cohort includes patients undergoing gender affirming surgery and surgical sperm retrieval. The mechanical properties, protein composition, RNA expression, and spatial protein expression (high-plex) have been comprehensively characterised. Analysis of the resulting datasets will continue until Q3 of 2025 and the resulting dataset will inform the development of representative models;
(ii) Developed materials that accurately represent the properties of testicular tissue. The material can be molded and printed into geometries that mimic the native geometries exhibited by human testicular tissue. Material characterisation and refinement will continue until Q4 of 2025;
(iii) Developed a system for fabricating miniaturised models of the testis at high-throughput. System refinement will continue until Q4 of 2026.
This project can advance the field of male reproductive health beyond the state of the art by providing a representative platform for evaluating treatments aimed at addressing male infertility. It can also provide a platform for maturing male germ cells in vitro to the point where the cells could be used for in vitro fertilisation. Such a platform would enable parenthood for adult men experiencing infertility due to germ cell maturation arrest, a common side effect of the treatment administered to combat childhood cancer.