Cornell University scientists have taken a major step toward developing a safe, reversible, long-acting and 100% effective nonhormonal male contraceptive, considered the holy grail of male contraception.
In a proof-of-principle study conducted in mice over six years, the team showed that interrupting a key step in meiosis, the process that produces sex cells, can temporarily halt sperm production without causing lasting harm.
The findings were published today (April 7) in the Proceedings of the National Academy of Sciences.
To achieve this, scientists used JQ1, a small molecule inhibitor originally developed to study cancer and inflammatory diseases. While JQ1 is not suitable as a treatment due to neurological side effects, it is known to interfere with a stage of meiosis called prophase 1. This allowed researchers to demonstrate, for the first time, that targeting meiosis can safely and reversibly shut down sperm production.
“We’re practically the only the group that’s pushing the idea that contraception targets in the testis are a feasible way to stop sperm production,” said Paula Cohen, professor of genetics and director of the Cornell Reproductive Sciences Center.
“Our study shows that mostly we recover normal meiosis and complete sperm function, and more importantly, that the offspring are completely normal,” Cohen said.
Why New Male Birth Control Options Are Needed
Current male contraceptive options remain limited to condoms and vasectomies. While vasectomies are considered long-term, many men hesitate to undergo the procedure, even though reversal surgery is sometimes possible. At the same time, researchers have been cautious about developing hormonal approaches, partly due to safety concerns observed in women.
Cohen and her team focused on meiosis rather than other stages of sperm development to ensure that sperm production could be fully stopped while still allowing it to recover later. This approach also preserves overall reproductive health.
“We didn’t want to impact the spermatogonial stem cells, because if you kill those, a man will never become fertile again,” Cohen said. Also, once sperm entered spermiogenesis, there was a potential for viable sperm to leak out and fertilize an egg.
How JQ1 Temporarily Disrupts Fertility
JQ1 works by disrupting meiosis during prophase 1, causing developing cells to die at that stage. It also blocks the gene activity required for later stages of sperm development.
In the study, male mice received JQ1 for three weeks. During this time, sperm production stopped completely, and key features of meiosis, including chromosome behavior during prophase 1, were disrupted.
Once the treatment ended, recovery began. Within six weeks, most normal meiotic processes returned, along with healthy sperm production. The researchers then bred the mice and confirmed that they were fertile. Their offspring were also healthy and able to reproduce.
“It shows that we recover complete meiosis, complete sperm function, and more importantly, that the offspring are completely normal,” Cohen said.
What a Future Male Contraceptive Could Look Like
If developed for human use, this type of male contraceptive could be delivered as an injection given every three months or possibly as a patch to maintain effectiveness, Cohen said.
