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.
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.
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Inpp5b-/- 小鼠雄性生殖功能的多变量分析揭示了生育力缺陷、精卵膜相互作用和精子 ADAM 蛋白水解的异质性。
DOI：
10.1093/molehr/gaq029
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发表时间：
2010
影响因子：
4
通讯作者：
Evans,JaniceP
中科院分区：
文献类型：
--
作者：
Marcello,MatthewR;Evans,JaniceP
Past work indicated that sperm from mice deficient in the inositol polyphosphate 5-phosphataseInpp5bhave reduced ability to fertilize eggsin vitroand 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 inInpp5b−/−mice. Multiple endpoints of reproductive functions [mating trials,in vitrofertilization (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 fromInpp5b−/−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 inInpp5b-null sperm. To our surprise and differing from previous reports, we found that ADAM cleavage was only modestly impaired in numerousInpp5b-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 theInpp5b−/−phenotype and also a blueprint for multivariate analysis to examine relationships between molecular characteristics andin vitroandin vivophysiological functions.
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