Multivariate analysis of male reproductive function in Inpp5b-/- mice reveals heterogeneity in defects in fertility, sperm-egg membrane interaction and proteolytic cleavage of sperm ADAMs.
Submitted by Matthew Marcello on
Title | Multivariate analysis of male reproductive function in Inpp5b-/- mice reveals heterogeneity in defects in fertility, sperm-egg membrane interaction and proteolytic cleavage of sperm ADAMs. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Marcello, MR, Evans, JP |
Journal | Mol Hum Reprod |
Volume | 16 |
Issue | 7 |
Pagination | 492-505 |
Date Published | 2010 Jul |
ISSN | 1460-2407 |
Keywords | ADAM Proteins, Animals, Female, Fertilins, Fertility, Immunoglobulins, Male, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Mutant Strains, Multivariate Analysis, Phosphoric Monoester Hydrolases, Sperm-Ovum Interactions, Spermatozoa |
Abstract | Past work indicated that sperm from mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b have reduced ability to fertilize eggs in vitro and reduced epididymal proteolytic processing of the sperm protein A Disintegrin and A Metalloprotease 2 (ADAM2). On the basis of these data, our central working hypothesis was that reduced ADAM cleavage would correlate with reduced sperm-egg binding and fusion and in turn with reduced male fertility in Inpp5b(-/-) mice. Multiple endpoints of reproductive functions [mating trials, in vitro fertilization (IVF) assays and ADAM2 and ADAM3 cleavage] were investigated on a male-by-male basis, with pair-wise correlation analysis used to assess the relationships between these various parameters. Motile sperm from Inpp5b(-/-) mice showed significantly reduced fertilization of zona pellucida-free eggs due to reduced binding to the egg plasma membrane and subsequent fusion. Localization of a mouse sperm protein required for gamete fusion, IZUMO1, appears normal in Inpp5b-null sperm. To our surprise and differing from previous reports, we found that ADAM cleavage was only modestly impaired in numerous Inpp5b-null males and varied between individual animals. Performance in mating trials also differed from past reports. The pair-wise correlation analysis revealed that ADAM2 and ADAM3 cleavage was positively correlated, suggesting that processing of these proteins occurs by related/identical mechanisms, but otherwise, there were few correlations between the reproductive endpoints examined here. Nevertheless, this work provides detailed analysis of the Inpp5b(-/-) phenotype and also a blueprint for multivariate analysis to examine relationships between molecular characteristics and in vitro and in vivo physiological functions. |
DOI | 10.1093/molehr/gaq029 |
Alternate Journal | Mol. Hum. Reprod. |
PubMed ID | 20403911 |
PubMed Central ID | PMC2882869 |
Grant List | R01 HD037696 / HD / NICHD NIH HHS / United States R01 HD037696-10 / HD / NICHD NIH HHS / United States T32 HD007276 / HD / NICHD NIH HHS / United States |