Researchers at Michigan State University in East Lansing have received two grants from the National Institutes for Health totaling $2.8 million to find the genes responsible for male fertility. They will use the funds to find the genes and regulatory pathways in mice that could lead to the development of new male fertility and contraception options for humans.
“We are studying genes and their encoded proteins in the piRNA pathway,” says Chen Chen, leader of the studies and associate professor of animal science in MSU’s College of Agriculture and Natural Resources. “Using genetic and biochemical manipulation, we will have a better understanding of how small RNAs control male fertility, the genetic cause of infertility, and how to potentially target the piRNA pathway for male contraception.”
Transposons, which can be described as parasites that affect genes, are kept in check by piRNAs, small RNA molecules that can recognize and destroy transposons. Poor sperm quality and quantity contribute to male infertility, but the genetic cause of male infertility is unclear. Mice are mammals and use many of the same genes for reproduction as humans.
One grant will focus on a large population of piRNAs unique to mammals whose function is not to silence harmful transposons but to promote fertility. This particular piRNA population is activated during the second phase of sperm creation.
The other grant will study a small RNA-based intracellular immune system that safeguards the germline genome. This immune system uses piRNAs as a guide to detect and destroy transposons. Without the system, transposon activity gets out of control, causing DNA damage, germ (reproductive) cell death, and male infertility.
“On one hand, infertility is a widespread reproductive health problem,” says Chen. “In fact, one in 10 couples are infertile, and male factors contribute to almost half of all infertility cases. On the other hand, male fertility needs to be controlled to prevent unintended pregnancy. A male birth control pill is unavailable, and the identification of novel male contraception targets is strongly desired.”