Identification of a New QTL Region on Mouse Chromosome 1 Responsible for Male Hypofertility: Phenotype Characterization and Candidate Genes.

Magalie Vatin,Ahmed Ziyyat,Virginie Firlej,Sandrine Barbaux,Xavier Montagutelli,Carmen Marchiol,Marie-Sophie Girault,Daniel Vaiman,Côme Ialy-Radio

doi:10.3390/ijms21228506

Abstract

Male fertility disorders often have their origin in disturbed spermatogenesis, which can be induced by genetic factors. In this study, we used interspecific recombinant congenic mouse strains (IRCS) to identify genes responsible for male infertility. Using ultrasonography, in vivo and in vitro fertilization (IVF) and electron microscopy, the phenotyping of several IRCS carrying mouse chromosome 1 segments of Mus spretus origin revealed a decrease in the ability of sperm to fertilize. This teratozoospermia included the abnormal anchoring of the acrosome to the nucleus and a persistence of residual bodies at the level of epididymal sperm midpiece. We identified a quantitative trait locus (QTL) responsible for these phenotypes and we have proposed a short list of candidate genes specifically expressed in spermatids. The future functional validation of candidate genes should allow the identification of new genes and mechanisms involved in male infertility.

Highlights

In approximately half of the 15% of couples that suffer from sterility, the cause is ascribed to male infertility, which encompasses a wide variety of syndromes
We have previously presented the generation of the subcongenic substrains from the 66HMMU1 strain by recombination events inside the MMU1 spretus segment [9]
We present the phenotyping of the Rc3 substrain compared to the B6 strain, by using an in vivo ultrasonic method to evaluate the implantation rate at E7.5 and E9.5

Summary

Introduction

In approximately half of the 15% of couples that suffer from sterility, the cause is ascribed to male infertility, which encompasses a wide variety of syndromes. Spermatogenesis is a biological process composed of a series of highly complex cellular events. It can be broadly divided into five discrete events: (1) renewal of spermatogonial stem cells and spermatogonia via mitosis, (2) proliferation (via mitosis) and differentiation of spermatogonia, (3) meiosis, (4) spermiogenesis (transformation of round spermatids into elongated spermatids and spermatozoa) and (5) spermiation, the release of sperm from the epithelium into the tubule lumen. All steps are highly regulated and dysfunctions in this key physiological process can result in infertility. Regulation of this complex process depends on the cooperation of many genes, which are expressed at these different steps [2]. Diverse cellular and molecular processes allow sperm head formation and organization. Mutant models have improved the understanding of the etiology of teratozoospermia and clarified some of the mechanisms involved in sperm head formation and organization [3]

Methods

Results

Conclusion