Abstract
BackgroundIn a previous work, using an interspecific recombinant congenic mouse model, we reported a genomic region of 23 Mb on mouse chromosome 11 implicated in testis weight decrease and moderate teratozoospermia (∼20–30%), a Quantitative Trait Locus (QTL) called Ltw1. The objective of the present study is to identify the gene underlying this phenotype.ResultsIn the present study, we refined the QTL position to a 5 Mb fragment encompassing only 11 genes. We showed that the low testis weight phenotype was due to kinetic alterations occurring during the first wave of the spermatogenesis where we could point out to an abnormal lengthening of spermatocyte prophase. We identify Fidgetin-like 1 (Fignl1) as the gene underlying the phenotype, since if fulfilled both the physiological and molecular characteristics required. Indeed, amongst the 11 positional candidates it is the only gene that is expressed during meiosis at the spermatocyte stage, and that presents with non-synonymous coding variations differentiating the two mouse strains at the origin of the cross.ConclusionsThis work prompted us to propose Fignl1 as a novel actor in mammal's male meiosis dynamics which has fundamental interest. Besides, this gene is a new potential candidate for human infertilities caused by teratozoospermia and blockades of spermatogenesis. In addition this study demonstrates that interspecific models may be useful for understanding complex quantitative traits.
Highlights
Fertility is an important concern both in human medicine, where 10–15% of the couples call for the services of assisted reproductive technologies, and for various domestic species of economic interest, such as dairy cows where a striking drop in fertility has been observed in recent years [1,2]
We present arguments suggesting that the role of this gene is to control male meiosis dynamic
In parallel with testis weight, the mean diameter of seminiferous tubules in 97 C mice was significantly smaller than this of B6 from 21 days post partum (DPP) (,7%) and this difference reached 25–30% thereafter (Figure 1b). Since this time period corresponds to the onset of the first wave of spermatogenesis, we examined in detail histological sections during this period and we quantified the seminiferous tubule sections according to the stage of the spermatogenesis cycle
Summary
Fertility is an important concern both in human medicine, where 10–15% of the couples call for the services of assisted reproductive technologies, and for various domestic species of economic interest, such as dairy cows where a striking drop in fertility has been observed in recent years [1,2]. The genetic basis of male infertilities is far from being completely elucidated and is mostly explained by deletions of the AZF region of the Y chromosome [3,4]. Such infertilities affect no more than 10% of the male patients, stressing the need of identifying new actors responsible for these disorders. Hundreds of genes involved in gametogenesis in a broad sense have been identified by gene-invalidation approaches in mice [5] While these experiments lead to a complete abolishment of gene expression, more quantitative approaches are of interest to identify new fertility genetic determinants. The objective of the present study is to identify the gene underlying this phenotype
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