Project No. 2462

STANDARD PROJECT

Primary Supervisor

Dr Ryohei Sekido – University of Portsmouth

Co-Supervisor(s)

Dr Anthony Lewis – University of Portsmouth

Dr Peter Ellis – University of Kent

Dr Seung Seo Lee – University of Southampton

Summary

Increased infertility rate is nowadays a significant issue in humans and animals, especially endangered species.

In humans, approximately 10-15% of couples require fertility treatment and 40% of the causes of their infertility are male factors. The present assisted reproductive technology, such as in vitro fertilisation and intracytoplasmic sperm injection, has only limited success in humans and animals. It is also notable that boys having chemotherapy treatment for cancer at young age often become sterile permanently because the cancer drug kills germ cells. To overcome the problem, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been considered as another source of sperm. To date, it is already possible to generate artificial primordial germ cells (PGCs), i.e. diploid gamete precursors, from human and mouse ESCs/iPSCs. However, despite many attempts using different conditioned media, no functional sperm has been generated from the artificial PGCs in vitro.

We propose that direct interaction between germ cells and testicular somatic cells is essential to sperm production as in the case of spermatogenesis in vivo. Hence, we previously generated germ cell progenitor-like cells and testicular somatic cell-like cells from mouse ESCs individually, and then co-cultured them in vitro. The unique culture system allowed us to demonstrate creation of a testicular organoid with the appearance of a structure reminiscent of the seminiferous tubule, in which an interaction of PGC-like cells and Sertoli cell-like cells was reconstructed, although the PGC-like cells did not differentiate into haploid sperm. In this project, we will apply multi-disciplinary approaches to the current organoid culture system including 3D culture, synthetic chemistry, and OMICS.  In vitro sperm generation will have an enormous impact on not only fertility treatment in humans and endangered animals, but also selective breeding of livestock.

The candidates should have interest in reproductive biology, stem cell biology and tissue engineering. Experience in cell culture and molecular biology would be desirable.