Calcineurin Inhibitors Reversibly Block Male Fertility In Mice

Blocking calcineurin in male mice makes them infertile reversibly. Could this be the beginnings of male oral contraceptives?

AsianScientist (Oct. 28, 2015) – To date, oral contraceptives for women have been developed and used worldwide, but, there are no oral contraceptives for men.

A group of researchers at Osaka University have found that sperm calcineurin deficient male mice are infertile. Furthermore, they observed that calcineurin inhibitors, cycloproins A and FK506, could reversibly affect male mouse fertility. Their work, published in Science, paves a way for the development of male contraceptives.

Global population is growing at an unprecedented rate. While women have a choice in controlling their fertility with contraceptive pills, male contraceptives are not yet available. The current study may be able to change this.

Calcineurin is a well-characterized calcium-dependent phosphatase and its inhibitors (CsA and FK506) have been clinically used for immunosuppression after organ transplantation. In toxicity tests using rats and mice, it has been reported that these drugs also impair male fertility.

Working in mouse models, the group, led by Professor Masahito Ikawa at Osaka University, has found that PPP3CC/PPP3R2 are specific forms of calcineurin that is expressed in the testis. Male mice lacking calcineurin has aberrant sperm motility and morphology. In particular, it affects the midpiece flexibility of a sperm during sperm production.

The group also found that wild type mice treated with calcineurin inhibitors such as Cyclosporine A (CsA) and FK506 became infertile within two weeks. Their fertility recovered within a week after the discontinuation of the drug treatment.

The findings of the group have laid foundations for future study in male infertility brought about by taking immunosupressant drugs in patients. In addition, the reversible block of calcineurins inhibitors on male fertility also opens avenues for the development of male contraceptives.

The article can be found at: Miyata et al. (2015) Sperm Calcineurin Inhibition Prevents Mouse Fertility with Implications for Male Contraceptive.


Source: Osaka University.
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