Mutagenesis-generated mouse models of human infertility with abnormal sperm

The aetiology of human male fertility, with impairment of sperm number, motility and morphology (oligoasthenoteratozoospermia), has been difficult to understand, partly for lack of animal models. METHODS: An ethylnitrosourea (ENU) mutagenesis strategy has been successful in producing heritable gene...

Full description

Saved in:
Bibliographic Details
Published in:Human reproduction (Oxford) 2007-01, Vol.22 (1), p.159-166
Main Authors: Lessard, C., Lothrop, H., Schimenti, J.C., Handel, M.A.
Format: Article
Language:English
Subjects:
Animals
Bacterial Proteins
Biological and medical sciences
Calcium-Binding Proteins
Disease Models, Animal
Ethylnitrosourea
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Infertility, Male - chemically induced
Infertility, Male - genetics
Male
Medical sciences
Mice
Mice, Inbred C57BL
Microscopy, Electron, Transmission
Mutagenesis
Phenotype
Spermatozoa - abnormalities
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The aetiology of human male fertility, with impairment of sperm number, motility and morphology (oligoasthenoteratozoospermia), has been difficult to understand, partly for lack of animal models. METHODS: An ethylnitrosourea (ENU) mutagenesis strategy has been successful in producing heritable gene mutations with phenotypes similar to human male infertility, and here, we describe three independent ENU-induced mutations that cause a phenotype of oligoasthenoteratozoospermia in mice. RESULTS: The loci identified by these three mutations are designated swm2, repro2 and repro3. All mutant males were characterized by low sperm concentration, poor sperm morphology and negligible motility, but the infertile males were apparently normal in other respects. Sperm from mutant males failed to fertilize oocytes in vitro. Ultrastructural analyses revealed varied abnormalities apparent in both testicular spermatids and epididymal sperm. Genetic mapping placed the swm2 gene on chromosome 7, the repro2 gene on chromosome 5 and the repro3 gene on chromosome 10. CONCLUSION: The single-gene mutations caused complex and non-specific sperm pathologies, a point with important implications for managing cases of human male infertility. The ultimate identification of the loci for the mutations causing these phenotypes will clarify aetiology of complex syndromes of infertility with sperm abnormalities consistent with oligoasthenoteratozoospermia.
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/del322