Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1.
Am J Hum Genet
; 87(4): 505-12, 2010 Oct 08.
Article
em En
| MEDLINE
| ID: mdl-20887963
ABSTRACT
One in seven couples worldwide are infertile, and male factor infertility accounts for approximately 30%-50% of these cases. Although many genes are known to be essential for gametogenesis, there are surprisingly few monogenic mutations that have been conclusively demonstrated to cause human spermatogenic failure. A nuclear receptor, NR5A1 (also called steroidogenic factor 1), is a key transcriptional regulator of genes involved in the hypothalamic-pituitary-steroidogenic axis, and it is expressed in the steroidogenic tissue of the developing and adult human gonad. Mutations of NR5A1 have been reported in 46,XY disorders of sex development and in 46,XX primary ovarian insufficiency. To test the hypothesis that mutations in NR5A1 cause male infertility, we sequenced NR5A1 in 315 men with idiopathic spermatogenic failure. We identified seven men with severe spermatogenic failure who carried missense mutations in NR5A1. Functional studies indicated that these mutations impaired NR5A1 transactivational activity. We did not observe these mutations in more than 4000 control alleles, including the entire coding sequence of 359 normospermic men and 370 fertile male controls. NR5A1 mutations are found in approximately 4% of men with otherwise unexplained severe spermatogenic failure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espermatogênese
/
Ativação Transcricional
/
Fator Esteroidogênico 1
/
Infertilidade Masculina
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França