Two drugs that help suppress the immune system in organ transplant patients may lead to a birth control “pill” for men that works by inhibiting the sperms’ ability to penetrate an egg, a new study has found.
The drugs – cyclosporine A (also known as CsA) and FK506 (also known as tacrolimus) – are given to transplant recipients to reduce the risk that the patient’s body will reject its new organ.
The drugs work by inhibiting an enzyme called calcineurin.
Researchers led by Haruhiko Miyata of Osaka University’s Research Institute for Microbial Diseases studied mice and identified a version of calcineurin that is found only in sperm.
This particular version contains a pair of proteins, called PPP3CC and PPP3R2.
Researchers created mice that were genetically altered to be unable to produce PPP3CC. These mice were referred to as the “knockout” animals.
Researchers found that when the knockout mice mated with females, the females did not get pregnant, ‘Los Angeles Times’ reported.
The team then performed in vitro fertilisation (IVF) using sperm from the knockout mice. The sperm were unable to fertilise an egg as long as the egg was covered by its usual layer of cumulus cells.
However, it wasn’t the cumulus cells that were the problem. In further tests, the researchers found that the sperm could make their way through these cells and bind to the zona pellucida, the membrane that surrounds the egg, but that was as far as they could go.
The sperm could not get through the membrane as they were deficient at something called “hyperactivation.” This is a particular type of movement that requires the sperm’s whip-like tail to beat back and forth with extra force.
Researchers found that the part of the sperm that connects the head to the tail was too rigid. That made the entire sperm cell too inflexible to move with enough force to penetrate the membrane.
The research team then gave the immunosuppressant drugs to regular mice, to see whether their sperm would turn out like the sperm of the knockout mice.
The drugs had no effect on mature sperm cells, which were just as flexible as ever, but worked better on sperm that were still developing.
Regular male mice that got either CsA or FK506 for two weeks became infertile, because the middle part of their sperm was rigid. Further tests showed that it took only four days for FK506 to render the mice infertile, and five days for CsA to do the same.
When the mice stopped taking the drugs, their fertility returned after one week.
“Considering these results in mice, sperm calcineurin may be a target for reversible and rapidly acting human male contraceptives,” researchers said.
The study was published in the journal Science.