The cause of male infertility in otherwise healthy men is a mystery that has dogged researchers for decades. But new research from the Oklahoma Medical Research Foundation points to a pair of genetic culprits.
In a paper published in the current issue of the Journal of Biological Chemistry, a team of OMRF researchers led by Kevin Moore, M.D., has found two proteins that could play a key role in male fertility. The new finding could have implications both for treating male infertility and developing new forms of male birth control.
Using gene “knockout” technology, Moore’s team created experimental mice that lacked an enzyme (known as TPST-2) they’d previously determined to be associated with infertility in the animals. “The knockout mice we made are perfectly capable of mating and creating motile sperm, but the sperm can’t bind with the egg to cause conception,” said Moore, the Fred Jones Distinguished Scientist at OMRF.
Taking these findings one step further, the team compared the genetically altered mice with normal mice. Moore’s lab discovered that in the mice that lacked the TPST-2 enzyme, two proteins—RNase 9 and Mfge8—were no longer modified properly. “We can’t say this is the reason for the infertility, but it’s intriguing.”
According to Moore, it is possible that when either of the proteins is missing or not modified properly by TPST-2, the mice are less fertile, but when both are missing, they are infertile. “There’s a chance that some infertile men are genetically unable to produce the TPST-2 enzyme,” said Moore. As a result, the RNase 9 and Mfge8 proteins they produce fail to function properly.
The new finding ultimately could lead to a pair of quite different applications in humans. “By adding the TPST-2 enzyme, we might be able to counteract infertility for some men. Conversely, blocking the enzyme could act as a non-hormonal male contraceptive,” he said.
But, Moore cautioned, there’s a long road ahead for the research. “We’ve only shown that the enzyme plays a role in fertility in mice. We still have to prove that TPST-2 plays a role in human fertility.”
Moore said the next step will be further studies of the proteins’ function in mice.
“This work is another step forward as we seek to understand male infertility,” said OMRF President Stephen Prescott, M.D. “Dr. Moore’s discovery could open the doors not only to a new treatment for male infertility but also to a novel male contraceptive. This is an exciting finding.”
The research was funded by a grant from the National Institute of Child Health and Human Development.