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Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive (Oct 2015)

science
Title:
Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive
Journal:
Science 23 October 2015: Vol. 350 no. 6259 pp. 442-445, DOI: 10.1126/science.aad0836
Author(s):
Miyata H1, Satouh Y1, Mashiko D2, Muto M3, Nozawa K2, Shiba K4, Fujihara Y1, Isotani A5, Inaba K4, Ikawa M6.
Author(s) affiliation:
1Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
2Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
3Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
4Shimoda Marine Research Center, University of Tsukuba, 5-10-1 Shimoda, Shizuoka 415-0025, Japan.
5Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
6Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. This email address is being protected from spambots. You need JavaScript enabled to view it..
 

 

Short description:
Unintended pregnancies are a major health issue worldwide. Although oral contraceptives were developed decades ago for use in women, there are no male oral contraceptives. Miyata et al. show that genetic deletion or drug inhibition of sperm-specific calcineurin enzymes in mice cause male sterility (see the Perspective by Castaneda and Matzuk). Although calcineurin inhibitors resulted in male infertility within 2 weeks, fertility recovered 1 week after halting drug administration. Because the sperm-specific calcineuin complex is also found in humans, its inhibition may be a strategy for developing reversible male contraceptives.
Link to the journal
 

 

Abstract taken from PubMed

Abstract:
Calcineurin inhibitors, such as cyclosporine A and FK506, are used as immunosuppressant drugs, but their adverse effects on male reproductive function remain unclear. The testis expresses somatic calcineurin and a sperm-specific isoform that contains a catalytic subunit (PPP3CC) and a regulatory subunit (PPP3R2). We demonstrate herein that male mice lacking Ppp3cc or Ppp3r2 genes (knockout mice) are infertile, with reduced sperm motility owing to an inflexible midpiece. Treatment of mice with cyclosporine A or FK506 creates phenocopies of the sperm motility and morphological defects. These defects appear within 4 to 5 days of treatment, which indicates that sperm-specific calcineurin confers midpiece flexibility during epididymal transit. Male mouse fertility recovered a week after we discontinued treatment. Because human spermatozoa contain PPP3CC and PPP3R2 as a form of calcineurin, inhibition of this sperm-specific calcineurin may lead to the development of a reversible male contraceptive that would target spermatozoa in the epididymis.
Copyright © 2015, American Association for the Advancement of Science.
Link to the paper on PubMed
Comment in:
DEVELOPMENTAL BIOLOGY. Toward a rapid and reversible male pill. [Science. 2015]
 




 

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