Proc. Natl. Acad. Sci. U S A 109:3850-3855 (2012)2012/03/06

In the present study, we showed that the testis specific protein disulfide isomerase homologue (PDILT) plays an indispensable role in the quality control of sperm membrane protein, ADAM3, in the endoplasmic reticulum. Pdilt -/- mice were male infertile because their spermatozoa lacking ADAM3 could not migrate through utero-tubal junction (A and B). However, the mutant spermatozoa were able to fertilize eggs when they were directly deposited into the oviduct (C and D). We would also like to call researchers' attention to the idea that the numerous sperm binding to the zona pellucida (ZP) surface of cumulus-free eggs could have been a “red herring” and less important than previously supposed. As we demonstrated in the present paper, at least in the mouse, the spermatozoa with defective ZP binding ability are able to fertilize cumulus-covered, ZP-intact eggs effectively. We believe this paper would provide basic information on the molecular mechanism of mammalian fertilization that may affect researchers’ and clinicians’ underlying philosophies.