Deletion of the Spata3 Gene Induces Sperm Alterations and In Vitro Hypofertility in Mice.

Marie-Sophie Girault,Ahmed Ziyyat,Côme Ialy-Radio,Rémi Pierre,Cécile Viollet,Sophie Dupuis,Laurence Stouvenel,Sandrine Barbaux,Maryline Favier

doi:10.3390/ijms22041959

Abstract

Thanks to the analysis of an Interspecific Recombinant Congenic Strain (IRCS), we previously defined the Mafq1 quantitative trait locus as an interval on mouse Chromosome 1 associated with male hypofertility and ultrastructural abnormalities. We identified the Spermatogenesis associated protein 3 gene (Spata3 or Tsarg1) as a pertinent candidate within the Mafq1 locus and performed the CRISPR-Cas9 mediated complete deletion of the gene to investigate its function. Male mice deleted for Spata3 were normally fertile in vivo but exhibited a drastic reduction of efficiency in in vitro fertilization assays. Mobility parameters were normal but ultrastructural analyses revealed acrosome defects and an overabundance of lipids droplets in cytoplasmic remnants. The deletion of the Spata3 gene reproduces therefore partially the phenotype of the hypofertile IRCS strain.

Highlights

Genes necessary for testis function, in post-meiotic germ cells, are extremely numerous [1]
We identified in an Interspecific Recombinant Congenic Strain (IRCS) a region of mouse chromosome 1 whose presence in a Mus spretus version within a Mus musculus domesticus (C57Bl/6) background is associated with signs reminiscent of globozoospermia
Spata3 Is Expressed in Sperm and Localized on the Acrosome

Summary

Introduction

Genes necessary for testis function, in post-meiotic germ cells, are extremely numerous [1]. The function and character of dispensability of these genes is only partially known. Their responsibility in clinical cases of human male infertility is only partially deciphered. Globozoospermia, a very rare form of male infertility characterized by round-shaped sperm heads that present a complete lack or an abnormal setup of their acrosome, can be explained by alterations of the DPY19L2 gene in about 60% of reported cases [2,3]. Some rare case reports have revealed mutations of the SPATA16, ZPBP1 and PICK1 genes [4,5,6]. The defect responsible for some remaining clinical cases is not yet identified and the biogenesis of the acrosome is still not completely elucidated. Animal models can help with suggesting some other genes involved in the process

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Results

Conclusion