Cornell Scientists Test a Reversible Male Contraceptive Approach

Cornell University scientists have reported a proof-of-principle step toward a reversible, long-acting, nonhormonal male contraceptive. In mice, they showed that blocking a natural checkpoint in meiosis can safely stop sperm production, then allow fertility to return after treatment ends.

The study, published in the Proceedings of the National Academy of Sciences, took six years to complete. The team used JQ1, a small molecule inhibitor originally developed as a research tool for cancer and inflammatory disease. Although it was not suitable as a therapy because of neurological side effects, it is known to interfere with prophase 1, a stage in meiosis. That made it useful for testing whether sperm production could be interrupted safely and reversed later.

“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 senior author Paula Cohen.  “Our study shows that mostly we recover normal meiosis and complete sperm function, and more importantly, that the offspring are completely normal,” Cohen added.

The work is aimed at a major gap in male contraception. Current options are condoms and vasectomies, and vasectomy is the only long-acting method available for men. Although it can be reversed through surgery, many men are hesitant to choose it. The researchers also wanted to avoid a hormonal approach, since hormonal contraceptives have raised safety concerns in women.

To preserve future fertility, the team chose to target meiosis rather than earlier or later stages of sperm development. Cohen said they did not want to affect spermatogonial stem cells, because damaging those cells would mean a man could never become fertile again. They also wanted to avoid allowing sperm to progress into spermiogenesis, where viable sperm might still be released. 

In the mouse study, male animals received JQ1 for three weeks. During treatment, they produced no sperm, and multiple molecular signs of meiosis were disrupted, including chromosome behavior during prophase 1. When the drug was stopped, healthy meiotic features returned within six weeks, and sperm production resumed normally. The mice were then bred and found to be fertile, and their pups were also fertile and healthy.

“It shows that we recover complete meiosis, complete sperm function, and more importantly, that the offspring are completely normal,” Cohen said.

A male contraceptive would likely start in the form of an injection taken every three months, or possibly a patch, to ensure effectiveness, Cohen explained.