Developing methods for the in vitro culture of testicular tissue for future fertility preservation (Professor Kevin Coward)

Childhood cancers are rare and account for 0.5% of all UK cancer cases; approximately 1900 new cases are diagnosed each year in the UK with boys more susceptible than girls.  However, the use of aggressive chemo- or radio-therapies can cause irreparable damage to the pre-pubertal gonad, thus resulting in sterility.  As assisted reproductive technology (ART) continues to expand on a global basis, fertility preservation for pre-pubertal children undergoing cancer treatment is becoming an increasingly attractive option. A DPhil project is available (subject to funding) to help us develop fertility preservation options for pre-pubertal boys. At this stage of life, the pre-pubertal testis has not yet started to produce functional sperm and it is therefore not possible to cryopreserve mature sperm, which represents the safest solution for adult males. Instead, appropriate methods must be devised which will allow immature testicular tissue to be safely frozen over long periods, and encourage the production of mature sperm from thawed testicular tissue by in vitro spermatogenesis which can then be used to rescue fertility via ART. Testicular organoids are three-dimensional in vitro models that mimic the native testicular microenvironment and have emerged as valuable research tools for male reproductive biology, offering insights into testicular development, spermatogenesis, and male reproductive disorders. This project aims to (a) devise methods to culture thawed testicular tissue in a manner which encourages and supports in vitro spermatogenesis, (b) create a perfused and environmentally-controlled three-dimensional (3D) scaffolding system to culture testicular tissue in order to provide the best possible chances of deriving functional sperm for ART, thus providing a platform from which to rescue fertility, and (c) investigate molecular strategies to deliver compounds to testicular cells to protect key cellular components against the detrimental effects of aggressive therapeutic regimes.

TRAINING OPPORTUNITIES