This confocal microscopic image of an 8-day-old mouse’s testicular section shows evidence of the PRC1 subcomponent Sall4 (in green). Scientists report in Genes & Development that PRC1 is the key molecular and genetic switch that activates production of healthy male sperm.

When it comes to male reproductive fertility, timing is everything.

Researchers at Cincinnati Children’s report in Genes & Development that a protein complex called Polycomb Repressive Complex 1 (PRC1) acts as a molecular switch that activates production of healthy male sperm—but only when the time is right. 

At birth, male mammals possess the germline cells needed to make sperm, but PRC1 represses activation during childhood. The new study, based on mouse models, shows that PRC1 changes at puberty, shedding the gene components that block sperm production and substituting in a component (Sall4) that starts 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,” says lead investigator Satoshi Namekawa, PhD, Division of Reproductive Sciences.

Future questions to explore include whether and how lifestyle or other environmental factors might affect this process; and whether Sall4 can serve as a biomarker for male infertility.