Male birth control injection causes reversible infertility in mice

A compound that renders sperm immobile has shown promise as a reversible form of contraception in mice.

The choices of birth control for men are limited to using condoms or having a vasectomy. “We definitely need more options,” says Martin Matzuk at Baylor College of Medicine in Texas.

Now, he and his colleagues have identified a potential new target — a protein expressed by the gene STK33 that is found in high concentrations in the testes of mice and men.

“In the absence of the STK33 protein, mice and human sperm wind up having very abnormal sperm tails, which causes motility defects,” says Matzuk. Studies have also shown that mice and men that lack or have a mutated version of the STK33 gene are infertile due to having malformed sperm.

To identify a compound that could bind to and inhibit the activity of the STK33 protein, the team combed through a library containing billions of chemicals, looking for a suitable molecule. Eventually, they found a candidate called CDD-2807.

Next, the team injected six male mice with CDD-2807 twice a day for 21 days and another seven male mice once a day for the same amount of time. After those three weeks, they housed all the male mice with females, while continuing the treatment for around another 40 days.

Only one mouse across both groups had impregnated a female by the end of the 40 days. That mouse only sired one pup, whereas mice litters typically have up to six pups, a sign that the treatment still reduced its fertility. No side effects were recorded. Three weeks after stopping the treatment, the researchers found that the mice’s infertility reversed and they were able to reproduce as normal.

Matzuk says they now hope to test an oral version of the treatment in primates.

Jochen Buck at Cornell University in New York says the paper is “very solid”, but that a not-yet-approved gel called NES/T, containing synthetic progesterone and testosterone, may work faster than targeting STK33 in people. The same would probably also be true for a contraceptive that targeted a protein known as retinoic acid receptor alpha, which is involved in sperm production, he says.