Stem cell findings raise hopes for male infertility therapies
Men are fertile throughout their lifespan because of the continual production of sperm in the testes, which is dependent on a small population of germline stem cells. But exactly which cells within the testes are functioning as stem cells has been controversial.
Monash Biomedicine Discovery Institute (BDI) scientists, led by Dr Robin Hobbs, have conducted a detailed study using mouse models that provides evidence that could solve this scientific riddle.
The research may lead to a way of treating men with infertility problems due to poorly functioning stem cells in the testes, and may act as a basis for developing a diagnostic tool to identify these men. It raises hopes of a therapy to counter the infertility that can result from treatments such as chemotherapy.
The study was published in Nature Communications.
Different schools of thought exist as to which cells in the testes are actually stem cell populations, with scientists often relying on different molecular markers to identify the cells they think are responsible.
“In this paper we performed a very detailed analysis of all immature cells in the testes to try to understand and reconcile all these different models of stem cell identity and behaviour to identify what the true stem cells are,” Dr Hobbs said.
“This is one of the first papers to do this,” he said.
The researchers looked at previously established stem cell markers to try to understand how they relate to one another. They also identified a new subset of cells, which are marked by the gene PDX1.
“We showed that this newly identified population of cells have very potent stem cell capabilities,” Dr Hobbs said.
The findings suggest that the stem cell system in the testes is flexible and dynamic.
“Some cell populations that are not normally acting as stem cells in the testes can actually be manipulated to become stem cells given the right environment,” he said.
This occurred when these cells were put in a culture heavily optimised to driving stem cell function. It also occurred when cells were transplanted into the testes, the study found.
The findings raised the possibility of regenerating sperm cells to aid in treatments for infertility.
“Infertility in men is a really complex disease, and can have many causes,” Dr Hobbs said.
“It’s thought that a subset of these infertility cases is due to poorly functioning stem cells. Our study tells us that many more cells in the testes could be forced to become stem cells that are not normally functioning as stem cells,” he said.
“It could help us devise ways to restore the germline of men who have poorly functioning stem cells or whose fertility was affected by treatments including chemotherapy.”
“We tried to resolve some of the controversies in the field and to our mind we’ve resolved them.”
Joint first authors on the paper were PhD student Mai La and Dr Juho-Antti Mäkelä. Monash BDI’s Professor Jose Polo and Dr Fernando Rossello contributed significantly, performing single-cell analyses.
Dr Hobbs, an ARC Future Fellow, is also head of the Germline Stem Cell Laboratory at the Australian Regenerative Medicine Institute (ARMI). The research was supported by Stem Cells Australia.
Read the full paper in Nature Communications titled Identification of dynamic undifferentiated cell states within the male germline.