Scientists at Cornell University have taken a major step toward developing a safe, reversible, long-acting, 100% effective non-hormonal male contraceptive, considered the holy grail of male contraception.
In a six-year proof-of-principle study conducted in mice, the researchers showed that interrupting a key step in meiosis, the process that produces sex cells, can temporarily stop sperm production without causing lasting harm.
The results of this survey were announced today (April 7th). Proceedings of the National Academy of Sciences.
To accomplish this, the scientists used JQ1, a small molecule inhibitor originally developed to study cancer and inflammatory diseases. Although JQ1 is not suitable for treatment due to neurological side effects, it is known to interfere with a meiotic phase called prophase 1. This allows researchers to demonstrate for the first time that sperm production can be stopped safely and reversibly by targeting meiosis.
“We are virtually the only group advancing the idea that intratesticular contraceptive targeting is a viable way to stop sperm production,” said Paula Cohen, professor of genetics and director of the Cornell Center for Reproductive Sciences.
“Our study shows that most restore normal meiosis and full sperm function, and more importantly, the offspring are completely normal,” Cohen said.
Why we need new male contraceptive options
Current male contraceptive options remain limited to condoms and vasectomies. Although vasectomy is considered long-term, many men are hesitant to undergo the procedure, even though a retrograde procedure may be possible. At the same time, researchers were cautious in developing the hormonal approach due to safety concerns observed in women.
Cohen and her team focused on meiosis, rather than other stages of sperm development, in order to completely stop sperm production but allow it to be restored later. This approach also maintains overall reproductive health.
“We didn’t want to affect the spermatogonial stem cells, because if you kill them, the man will never be able to reproduce again,” Cohen said. Also, once the sperm enters spermatogenesis, viable sperm can leak out and fertilize the egg.
How JQ1 temporarily interferes with fertility
JQ1 functions by disrupting meiosis during prophase 1, killing developing cells at that stage. It also blocks gene activity required for later stages of sperm development.
In this study, male mice were administered JQ1 for 3 weeks. During this period, sperm production ceased completely and key features of meiosis, including the behavior of chromosomes during prophase 1, were disrupted.
Once treatment was completed, recovery began. Within six weeks, most normal meiotic processes returned and healthy sperm were produced. The researchers then bred the mice and confirmed that they were fertile. Their offspring were also healthy and able to reproduce.
“This shows that meiosis has fully recovered, sperm function has fully recovered, and, more importantly, the offspring are completely normal,” Cohen said.
What will the male contraceptive pill of the future look like?
If developed for humans, this type of male contraceptive could be given as an injection every three months or, in some cases, as a patch to maintain effectiveness, Cohen said.
