Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive.
Science
; 350(6259): 442-5, 2015 Oct 23.
Article
em En
| MEDLINE
| ID: mdl-26429887
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tacrolimo
/
Ciclosporina
/
Anticoncepcionais Masculinos
/
Calcineurina
/
Fertilidade
/
Inibidores de Calcineurina
/
Infertilidade Masculina
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Science
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Japão