Models for male infertility: the t haplotypes

Area of Science:

• Genetics
• Reproductive Biology
• Developmental Biology

Background:

• The t haplotypes are variant alleles on mouse Chromosome 17, characterized by inversions.
• These haplotypes are known to cause male sterility in mice, while females remain fertile.

Purpose of the Study:

• To investigate the genetic basis of male sterility associated with t haplotypes in mice.
• To identify specific genes within the t haplotypes responsible for sperm dysfunction and fertilization defects.

Main Methods:

• Analysis of mice carrying Mus spretus-Mus domesticus recombinant Chromosomes 17.
• Examination of sperm motility and penetration ability in zona pellucida-free oocytes.
• Investigation of haploid gene expression in t-bearing spermatids.

Main Results:

• Males with two t haplotypes are sterile, exhibiting severe sperm motility defects.
• Males with one t haplotype (t/+) show mild motility deficits and delayed oocyte penetration.
• Spermatozoa not carrying the t haplotype in t/+ males are functionally impaired compared to t-bearing sperm.

Conclusions:

• Genes within the t haplotype inversions contribute to male sterility through sperm dysfunction.
• Haploid gene expression in t-bearing spermatids likely plays a role in the observed fertilization defects.
• Studying t haplotype sterility in mice offers insights into the genetic underpinnings of human sperm dysfunction.