Association of mutations in the zona pellucida binding protein 1 (ZPBP1) gene with abnormal sperm head morphology in infertile men.
Mol Hum Reprod
; 18(1): 14-21, 2012 Jan.
Article
in En
| MEDLINE
| ID: mdl-21911476
ABSTRACT
Nearly 7% of men are afflicted by male infertility worldwide, and genetic factors are suspected to play a significant role in the majority of these patients. Although sperm morphology is an important parameter measured in the semen analysis, only a few genetic causes of teratozoospermia are currently known. The objective of this study was to define the association between alterations in the genes encoding the Golgi-associated PDZ- and coiled-coil motif containing protein (GOPC), the protein interacting with C kinase 1 (PICK1) and the acrosomal protein zona pellucida binding protein 1 (ZPBP1/sp38) with abnormal sperm head morphology in infertile men. Previous reports demonstrated that mice lacking Gopc, Pick1 and Zpbp1 are infertile due to abnormal head morphology. Herein, using our validated RNA-based method, we studied spermatozoal cDNA encoding the human GOPC, PICK1 and ZPBP1 genes in 381 teratozoospermic and 240 controls patients via direct sequencing. Among these genes, we identified missense and splicing mutations in the sperm cDNA encoding ZPBP1 in 3.9% (15/381) of men with abnormal sperm head morphology. These mutations were not observed in 240 matched controls and the dbSNP database (χ(2) = 9.3, P = 0.002). In contrast, statistically significant and functionally relevant mutations were not discovered in the GOPC and PICK1 genes. In our study ZPBP1 mutations are associated with abnormal sperm head morphology, defined according to strict criteria, resembling the mouse Zpbp1 null phenotype. We hypothesize that missense mutations exert a dominant-negative effect due to altered ZPBP1 protein folding and proteinprotein interactions in the acrosome.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sperm Head
/
Egg Proteins
/
Infertility, Male
/
Membrane Proteins
/
Mutation
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Mol Hum Reprod
Journal subject:
BIOLOGIA MOLECULAR
/
MEDICINA REPRODUTIVA
Year:
2012
Document type:
Article
Affiliation country:
Estados Unidos