The key molecular and genetic switch that activates production of healthy male sperm has been identified by researchers at Cincinnati Children's Hospital Medical Center.
The mechanism, they report in Genes & Development, is a protein complex called Polycomb Repressive Complex 1 (PRC1).
When male mammals such as humans and mice are born, they come with all the reproductive germline cells needed to help make healthy fertile sperm and offspring. But the sperm isn't fertile during infancy or childhood. PRC1 tamps down specific genes and the activation of fertile sperm production until an individual reaches reproductive age.
In the current study it was discovered that when mice reach reproductive age, the PRC1 protein complex changes. It sheds reproductive germline gene components that block fertile sperm production and substitutes in a component (Sall4) that start spermatogenesis.
"A long-standing question has been how reproductive germline genes are activated in a precise and timely manner. Our study answers this fundamental question by identifying novel epigenetic machinery that directs timely activation of spermatogenesis," said Satoshi Namekawa, Ph.D., lead study investigator and member of the Division of Reproductive Sciences in the Cincinnati Children's Perinatal Institute. "This has a very high impact because we found that this repressor of sperm production, PRC1, has a new function by promoting gene activation to make sperm when the time comes."
The scientists also found that when PRC1 is disrupted, such as in male mice bred to not express PRC1, the animals have smaller testes and are unable to produce healthy sperm or offspring. Researchers still need to find out precisely how or why PRC1 changes its role from sperm suppressor to activator.
The current study opens the door to asking intriguing new questions about how lifestyle or other environmental factors might affect a male's reproductive capabilities through epigenetics, or how environmental factors can turn genes on or off in the body, Namekawa said. The findings also provide an opportunity to determine whether PRC1 or one of its genetic/molecular partners (like Sall4) can be useful as clinical biomarkers for male infertility.
Image: Confocal microscopic image of an 8-day-old mouse's testicular section shows evidence of the PRC1 subcomponent Sall 4 (in green). PRC1 was found to be the key molecular and genetic switch that activates production of healthy male sperm, an important clue to understanding the causes of male infertility or congenital illness. Image courtesy of Cincinnati Children's.