Male contraception pill may be possible soon, thanks to a veterinarian

Cornell is pioneering an innovative alternative to the oral contraceptive pill: male contraception that targets a mechanism in the early stage of sperm cell production.

One of the most common forms of birth control is the oral contraceptive pill. Yet for all its popularity, it hasn’t changed much since it was first introduced in the 1950s, according to Dr. Paula Cohen, professor of genetics at the Cornell University College of Veterinary Medicine. It is still hormone-driven, and can still induce a host of physiological problems, from blood clots and cardiovascular issues to increased breast cancer rates. It also still places the responsibility of family planning solely on women.

“Male contraception is not an area that’s been investigated much,” said Cohen, director of the Cornell Reproductive Sciences Center and associate vice provost for life sciences at Cornell.

The specific biological process Cohen has targeted for a potential male contraceptive is meiosis, a stage in early spermatogenesis in which a cell undergoes two rounds of division, resulting in four non-identical sperm cells, each of which contains half the number of chromosomes of the original “mom and pop” cell. Should the sperm fertilize an egg, this halved DNA content would pair up with an egg containing an equal amount of DNA to create an embryo with a full set of chromosomes.

This is a fraught process: for human men, about 1 in a 100 of their sperm have the wrong number of chromosomes, and the numbers are exponentially worse for women. “If you look in women, about 1 out of every 2 of their eggs has a wrong number of chromosomes,” Cohen said.

Dr. Paula Cohen, professor of genetics at the Cornell University College of Veterinary Medicine

The reason female meiosis is so much more error prone than male meiosis is that men have a built-in “monitoring system” that eradicates any erroneous cell, so those sperm never get produced. Cohen and her lab intend to use that knowledge to identify genes that control meiosis in mouse models, so the researchers can install “a big on/off switch” on the mice genes via genome-editing technology, and then control spermatogenesis. The insights they gain into that mechanism could ultimately inform the development of a form of contraception for human males that is not only reliable, but also reversible.

A second, and equally crucial, step is finding a way to experiment with spermatogenesis in a culture system. That’s necessary because meiosis is too complicated to study in vivo, i.e., in multicellular organisms, where there’s so many other ongoing biological processes that get in the way. Until now, a robust culture system for spermatogenesis has been impossible to create.

“The conditions for each stage are very specific,” Cohen said. “But I just want to culture them from spermatogonia into meiosis, a small fraction of the overall process. And if I could get that happening robustly, again and again and again, then I can look for genes, and from genes I can find targets. And from targets, I can develop drugs.”

Written by David Nutt; the full version of this article appears on the Cornell Chronicle website.