Dr Mahesh Sangrithi at his Reproductive Biology and Stem Cells laboratory, established in 2018 for Obstetrics and Gynaecology-related research.

 

Difficulties with conceiving a child affects 1 in 6 couples, and nearly half of them will have an underlying male factor. Recently, a decline in fertility has been noticed globally and this is associated at least in part with declining sperm parameters. Why this is the case is still poorly understood, as male fertility can have a number of underlying factors, such as general health of the man, smoking, and genetic constitution (e.g. sex chromosomes).

A recent study, led by Dr Mahesh Sangrithi, Consultant, Division of Obstetrics and Gynaecology (KK Women’s and Children’s Hospital), analysing the generation of sperm in the cynomolgus macaque, humans and mice, has found evolutionarily conserved gene expression profiles. Using single-cell transcriptional profiling technology, a comprehensive molecular 'atlas' of sperm production was established, including similarities and differences across the three species.

Such highly conserved genes are expected to play critical functions in the process of sperm development, and are therefore important candidates in male infertility. The team had analysed testis germline stem cells across the three mammalian species to identify molecular factors that drive the sperm production process.

“We are looking at characterising germ line stem cells in the testis, as their health is critical to lifelong sperm production in males and the generation of healthy offspring. We are also seeking a deeper understanding of how sex chromosome (X and Y) encoded genes specifically express during the process of sperm production, as these have specialised functions in male germ cells,” shares Dr Sangrithi.

“At a molecular level, this information can aid us in developing a more detailed understanding of 'roadblocks' during sperm production which can result in human male infertility,” adds Dr Sangrithi.

Looking forward, the team aims to focus on developing methods to isolate, store and expand testis germline stem cells, and methods of deriving in vitro sperm production culture systems. These stem cells may be very useful in the context of preserving male fertility.

Dr Sangrithi explains, “The more we are able to uncover about the biology underlying germ cells, the better we will be able to inform and manage not just patients with infertility, but also those with sex chromosome disorders.”

Read the full paper here