Cornell Scientists Advance Nonhormonal Male Contraception Research

Scientists at Cornell University have made significant progress toward developing a safe, reversible, long-acting, and 100% effective nonhormonal male contraceptive.

A proof-of-principle study conducted in mice, spanning six years, demonstrated that targeting a natural checkpoint in meiosis, the process of sex cell reproduction, can safely halt sperm production.

The findings were published in the Proceedings of the National Academy of Sciences.

The JQ1 Breakthrough

Researchers utilized JQ1, a small molecule inhibitor initially developed for cancer and inflammatory disease research. While JQ1 was not suitable as a final contraceptive due to neurological side effects, its ability to disrupt prophase 1, a stage of meiosis, allowed researchers to establish that meiosis and sperm production can be targeted safely and reversibly.

According to Paula Cohen, professor of genetics and director of the Cornell Reproductive Sciences Center, the study showed that normal meiosis and sperm function largely recover, and the offspring produced are completely normal.

Current Landscape and Research Goals

Existing male contraceptive options include condoms and vasectomies. Vasectomies, the only long-acting method for men, are technically reversible through surgery. The development of hormonal contraceptives for men has been approached cautiously due to potential dangers observed in women's hormonal treatments.

Cohen and her team focused on targeting meiosis to achieve a complete and reversible halt in sperm production without affecting other male functions. The objective was to avoid impacting spermatogonial stem cells, which are crucial for maintaining fertility, and to prevent viable sperm from potentially fertilizing an egg once spermiogenesis began.

How JQ1 Works

JQ1 functions by disrupting meiosis through cell death during prophase 1 and inhibiting gene expression necessary for spermiogenesis.

Proof-of-Principle Study Details

In the study, male mice received JQ1 for three weeks, resulting in no sperm production and disrupted molecular parameters of meiosis, including chromosomal behavior during prophase 1. Upon cessation of JQ1 administration, normal sperm production and most healthy prophase 1 parameters returned within six weeks. The researchers then successfully bred these mice, confirming their fertility and the health of their offspring. The pups were also found to be fertile.

Future Outlook

Cohen suggested that a future male contraceptive based on this research might be administered via a quarterly injection or a patch to ensure effectiveness.