Models for male infertility: the t haplotypes.

Abstract

The t haplotypes are variant alleles of genes in the proximal region of mouse Chromosome 17, linked together by four inversions. While females carrying two t haplotypes are fertile, males are sterile. Their spermatozoa exhibit severe motility defects and are unable to penetrate zona pellucida-free oocytes. Spermatozoa from males carrying one t haplotype (t/+) exhibit mild motility deficits and a delay in penetration of the zona-free oocyte. The inversions of the t haplotypes contain several genes that cause or contribute to male sterility, at least some of which can be identified by analysis of mice carrying Mus spretus-Mus domesticus recombinant Chromosomes 17. The t haplotypes specify a number of sperm biochemical abnormalities, but these have not been related directly to defects in fertilization. In t/+ males, spermatozoa not bearing the t haplotype are defective in fertilization compared with t-bearing spermatozoa. The mechanism causing this is likely to involve haploid gene expression confined to the t-bearing spermatids. Since many genes situated in the region of the t haplotypes have human homologues, an understanding of t haplotype sterility in mice is expected to contribute significantly to our knowledge of the genetic basis for human sperm dysfunction.