The search for a suitable male contraceptive has been long and mostly fruitless. Though ideas ranging from hormonal treatments to plugs inserted into the vas deferens have been proposed, none has yet made it to market, and men still rely on either condoms or vasectomies to prevent unwanted pregnancies. A new method interferes with genes responsible for creating new sperm, which could be a more attractive approach.
Snipping out a gene that regulates a key process in the maturation of sperm in mice renders them infertile, found researchers from Michigan State University, a discovery that could pave a path for a male contraceptive based on gene editing.
They pinned down the function of an enzyme called PNLDC1 that helps to keep so-called “jumping genes” in check during the production of new sperm. Jumping genes, also known as transposons, can copy themselves to other random parts of the genome, potentially causing harmful mutations. A small bit of RNA normally keeps them in check in the testes, and the researchers found that removing PNLDC1 prevented RNA from doing its job. By taking out the gene responsible for producing PNLDC1 in mice with CRISPR, researchers inhibited the production of healthy sperm and rendered the mice infertile. The research was published Tuesday in Nature Communications.
There didn’t seem to be any side effects to removing the enzyme, aside from the fact that the mice had slightly shrunken testes. The issue of side effects crops up often in studies of male contraceptives — it derailed a prominent World Health Organization-sponsored trial last year, and similar cases have made pharmaceutical companies wary of pursuing birth control for men. One of the main issues with male contraceptives is that many rely on testosterone to disrupt sperm production, a hormone already used to treat other conditions, but which can lead to mood swings and weight gain, among other problems.
Snipping out a gene involved in sperm production, and only sperm production, offers a more elegant approach. In addition, such a solution wouldn’t involve invasive surgeries, and would be a one-time solution. Some proposed male birth control treatments require daily pills, semi-annual injections or implants placed beneath the skin that need to be occasionally exchanged. For men that don’t want the hassle of remembering to take pills or visit the doctor to renew their birth control, gene editing could be far simpler.
That being said, this trial took place in mice. The effects of editing this particular gene in humans are unknown. Gene editing with CRISPR in humans is still in the very early stages, and it would likely be years before any gene editing contraceptive trials in humans got underway. What’s more, gene editing may not be an acceptable solution for everyone. For some men, reliable contraception may not be worth tinkering with their genomes.
A treatment based on this method wouldn’t necessarily need to involve gene editing, however, points out John Amory, a contraceptive researcher at the University of Washington. Now that researchers know what PNLDC1 does, they could potentially develop an inhibitor that targets the enzyme and disrupts its function. Even a more conventional treatment like this would still need to be examined for side effects, though.
“What would PNLDC1 inhibition do to the function of other tissues, and what problems would it cause?” Amory asked in an email to Discover. “The processes involved in sperm production are important elsewhere in the body.”
There’s also the question of reversibility. If we can’t undo a male contraceptive treatment, it’s no better than a vasectomy. The researchers didn’t test for reversibility here, but they would need to show that they could do it, and that sperm returned to normal levels afterward. Some previous options for male birth control, like the herb gossypol, tested in the 1970s, effectively lowered sperm counts, but proved to permanently affect sperm production in some men.
Nevertheless, studies have consistently shown that a majority of men would be interested in contraception for themselves. Gene editing could be just one of the many ways that men someday take responsibility for their sex lives.