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Scientists identify potential birth control 'pill' for men
Two drugs that help suppress the immune system in organ transplant patients may have a future as the long-sought birth control "pill" for men, new research suggests. 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. They work by preventing the immune system from making a protein that would otherwise mobilize T-cells to attack. Specifically, they do this by inhibiting an enzyme called calcineurin. By studying mice, researchers in Japan identified a version of calcineurin that is found only in sperm. This particular version contains a pair of proteins, called PPP3CC and PPP3R2.
To figure out what these proteins do, the researchers created male mice that were unable to make the PPP3CC protein (and thus produced less of the PPP3R2 protein). Then they studied the "knockout" animals to see how they were different from regular mice. The knockout mice still had sex with female mice, but the females didn't become pregnant. The absence of PPP3CC must be making the males infertile, the researchers figured. So they set about figuring out why.
They found that sperm from the knockout mice were able to reach the part of the ovary where eggs are usually fertilized. Although the number of sperm that completed the journey was lower than in regular mice, it wasn't low enough to explain the infertility. So they performed in vitro fertilization using sperm from the knockout mice. The sperm were unable to fertilize an egg as long as the egg was covered by its usual layer of cumulus cells. But 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, or ZP, the membrane that surrounds the egg. But that was as far as they could go.
Two drugs that help suppress the immune system in organ transplant patients may have a future as the long-sought birth control "pill" for men, new research suggests. 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. They work by preventing the immune system from making a protein that would otherwise mobilize T-cells to attack. Specifically, they do this by inhibiting an enzyme called calcineurin. By studying mice, researchers in Japan identified a version of calcineurin that is found only in sperm. This particular version contains a pair of proteins, called PPP3CC and PPP3R2.
To figure out what these proteins do, the researchers created male mice that were unable to make the PPP3CC protein (and thus produced less of the PPP3R2 protein). Then they studied the "knockout" animals to see how they were different from regular mice. The knockout mice still had sex with female mice, but the females didn't become pregnant. The absence of PPP3CC must be making the males infertile, the researchers figured. So they set about figuring out why.
They found that sperm from the knockout mice were able to reach the part of the ovary where eggs are usually fertilized. Although the number of sperm that completed the journey was lower than in regular mice, it wasn't low enough to explain the infertility. So they performed in vitro fertilization using sperm from the knockout mice. The sperm were unable to fertilize an egg as long as the egg was covered by its usual layer of cumulus cells. But 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, or ZP, the membrane that surrounds the egg. But that was as far as they could go.
