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1 October 2003 Loss of Nectin-2 at Sertoli-Spermatid Junctions Leads to Male Infertility and Correlates with Severe Spermatozoan Head and Midpiece Malformation, Impaired Binding to the Zona Pellucida, and Oocyte Penetration
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Abstract

The members of the nectin/CD155 gene family represent a growing class of novel cell adhesion molecules of the immunoglobulin superfamily. In the present study, we describe the generation of a mouse line lacking a functional nectin-2 gene (nectin-2LacZ/LacZ) and analyze the resulting male-specific infertility phenotype. Although nectin-2LacZ/LacZ males produced normal amounts of motile spermatozoa, scanning electron microscopy revealed severe malformations of the spermatozoan head and midpiece. Besides a 4-fold reduction in migration of nectin-2LacZ/LacZ spermatozoa to the oviducts, in vitro binding to zona-intact mouse oocytes was reduced 6-fold. On the other hand, nectin-2LacZ/LacZ spermatozoa bound to zona-free hamster oocytes at near-wild type levels but, remarkably, failed to penetrate. In addition to the previously reported expression of nectin-2 and nectin-3 at Sertoli-spermatid junctions and of nectin-2 at inter-Sertoli cell junctions, we also found nectin-2 to localize at apical cell-cell junctions of the epididymal epithelium. Expression analysis of a LacZ knockin gene into the defunct nectin-2 gene in nectin-2LacZ/LacZ mice provided additional support for our earlier conjecture that in normal testis, nectin-2 is produced exclusively by Sertoli cells. Finally, we found Sertoli-spermatid junctions in nectin-2LacZ/LacZ mice to be virtually devoid of the actin-bundling protein espin, suggesting that ectoplasmic specializations fail to form in the absence of nectin-2. Our functional analyses indicate that the infertility phenotype of nectin-2-deficient male mice is caused by a combination of reduced migration to the oviduct, spermatozoa-zona binding, and sperm-oocyte fusion. We corroborate our previous description of a heterotypic adhesion complex between Sertoli cells and elongated spermatids that is maintained by nectin-2 and nectin-3, respectively.

Steffen Mueller, Thomas A. Rosenquist, Yoshimi Takai, Richard A. Bronson, and Eckard Wimmer "Loss of Nectin-2 at Sertoli-Spermatid Junctions Leads to Male Infertility and Correlates with Severe Spermatozoan Head and Midpiece Malformation, Impaired Binding to the Zona Pellucida, and Oocyte Penetration," Biology of Reproduction 69(4), 1330-1340, (1 October 2003). https://doi.org/10.1095/biolreprod.102.014670
Received: 14 December 2002; Accepted: 1 May 2003; Published: 1 October 2003
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