A new target for the development of male contraceptives
Japanese scientists have come close to creating a male contraceptive
Daniil Kuznetsov, N+1
A group of Japanese physiologists and biochemists have learned to reduce sperm motility in male mice by "disabling" the motility of the middle part of the sperm (connecting the tail and head). This was achieved by inhibiting the action of the calcineurin protein, which has enzymatic properties and is produced in the testicles. The work was published in the journal Science (Haruhiko Miyata et al., Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive).
Intensive movements of the tail of spermatozoa are a key factor ensuring their mobility, the ability to reach the egg, penetrate into it and fertilize. Weak mobility of the tail, in fact, means infertility of the seed. This can be achieved by making the middle part of the sperm rigid, to which the tail is attached. Previously, it was already known that some immunosuppressants – drugs that artificially inhibit immunity, such as Tacrolimus or Cyclosporine A (used in organ and tissue transplantation) can, as a side effect, inhibit the calcineurin protein, presumably involved in the regulation of the motility of this part of the sperm.
The full role of calcineurin (calcium-dependent serine/threonine phosphatase) has not yet been studied. There is evidence that a special form of it is contained in sperm cells. Japanese scientists have knocked out the calcineurin gene in male mice. As a result, they turned out to be completely infertile due to low sperm motility.
Then another group of adult males with proven fertility were injected with Tacrolimus (FK506) and Cyclosporine A (CsA), which eventually led to similar sperm defects on 4-5 days after the introduction of immunosuppressants.
Diagram from an article in Science – VM
Fertility returned to males again a week after stopping taking immune-suppressing medications.
Calcineurin in humans is similar in structure to a type of this protein in mice. According to Japanese researchers, this gives a potential opportunity to create a similar drug that temporarily suppresses the male ability to fertilize. Also, this discovery may help in the creation of new types of therapies for the treatment of male infertility.
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15.10.2015