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Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive.
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- Additional Information
- Source:
Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
- Publication Information:
Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
- Subject Terms:
- 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.)
- Comments:
Comment in: Science. 2015 Oct 23;350(6259):385-6. (PMID: 26494747)
- Accession Number:
0 (Calcineurin Inhibitors)
0 (Contraceptive Agents, Male)
0 (PPP3R2 protein, mouse)
83HN0GTJ6D (Cyclosporine)
EC 3.1.3.16 (Calcineurin)
EC 3.1.3.16 (PPP3CC protein, mouse)
WM0HAQ4WNM (Tacrolimus)
- Publication Date:
Date Created: 20151003 Date Completed: 20160328 Latest Revision: 20220321
- Publication Date:
20221213
- Accession Number:
10.1126/science.aad0836
- Accession Number:
26429887
No Comments.