Scientists Discover a Reversible Method of Contraception for Men that Stops Sperm Production

Scientists at Cornell University have taken a crucial step toward developing a safe, reversible, long-acting, and 100% effective non-hormonal contraceptive for men, which is considered the “holy grail” of male contraception. In a proof-of-principle study conducted over six years in mice, the team demonstrated that interrupting a key step in meiosis—the process by which sex cells are formed—can temporarily halt sperm production without causing permanent damage. The results were published in the Proceedings of the National Academy of Sciences.

Inhibiting Sperm Production

To achieve this, the scientists used JQ1, a small-molecule inhibitor originally developed for research into cancer and inflammatory diseases. Although JQ1 is not suitable as a therapy due to neurological side effects, it is known to interfere with a phase of meiosis known as prophase 1. This allowed the researchers to demonstrate for the first time that targeted manipulation of meiosis can safely and reversibly halt sperm production.

“We are practically the only group advancing the idea that targeting the testes is a viable way to stop sperm production,” said Paula Cohen, professor of genetics and director of the Cornell Reproductive Sciences Center. “Our study shows that in most cases we can restore normal meiosis and full sperm function, and, more importantly, that the offspring are completely normal,” said Cohen.

Why New Contraceptive Options for Men Are Needed

Current contraceptive options for men remain limited to condoms and vasectomies. While vasectomies are considered a long-term solution, many men are reluctant to undergo the procedure, even though reversal 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 completely halted while still allowing for recovery later. This approach also preserves overall reproductive health. “We didn’t want to compromise the spermatogonial stem cells, because if you kill those, a man will never be fertile again,” said Cohen. Furthermore, once sperm had entered spermatogenesis, there was a risk that viable sperm could escape and fertilize an egg.

How JQ1 Temporarily Halts Fertility

JQ1 works by interrupting meiosis during prophase 1, causing developing cells to die at this 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 came to a complete halt, and key features of meiosis, including chromosome behavior during prophase 1, were disrupted.

Recovery began once treatment ended. Within six weeks, most normal meiotic processes returned, as did the production of healthy sperm. The researchers then bred the mice and confirmed that they were fertile. Their offspring were also healthy and capable of reproduction. “This shows that we can restore full meiosis and full sperm function and, more importantly, that the offspring are completely normal,” said Cohen. If developed for human use, this type of male contraceptive could be administered as an injection every three months or possibly as a patch to maintain efficacy, said Cohen.