Some Single Nucleotide Polymorphisms of MSY2 Gene Might Contribute to Susceptibility to Spermatogenic Impairment in Idiopathic Infertile Men

doi:10.1016/j.urology.2007.12.055

Urology

Volume 71, Issue 5, May 2008, Pages 878-882

https://doi.org/10.1016/j.urology.2007.12.055 Get rights and content

Objectives

To explore the possible association of the MSY2 gene with idiopathic male infertility in humans.

Methods

Mutation screening was performed in 326 patients with azoospermia or severe oligospermia and 210 controls by denaturing high-performance liquid chromatography and DNA sequencing. The differences in genotype and allele distribution in the two groups were evaluated. The Haploview program, version 4.0, was used to perform linkage disequilibrium and haplotype analysis.

Results

A total of eight variations, including five single nucleotide polymorphisms and three rare single nucleotide changes, were identified. The frequencies of allele C of c.187T>C and allele G of c.1095+16A>G were significantly greater in the controls than in the patients, and both seemed to play a protective role against spermatogenic impairment. The haplotype GTCTA, consisting of the five single nucleotide polymorphisms, might be a genetic risk factor for development of male infertility.

Conclusions

The results of our study suggest that some polymorphisms of the MSY2 gene might be associated with impaired spermatogenesis and that the gene could also be involved in modifying the susceptibility to idiopathic spermatogenic impairment in humans.

Section snippets

Study Participants

All participants, who were genetically unrelated Han men, were recruited from Sichuan province, southwest China. The institutional ethic review board of West China Hospital, Sichuan University approved this study, and all subjects provided informed consent. A total of 326 idiopathic infertile patients, 25 to 40 years old, including 220 men with azoospermia and 106 men with severe oligospermia (less than 5 × 10⁶ sperm/mL). All had undergone semen analyses according to the World Health

Results

In total, eight variations were found, and all of them were single nucleotide changes by screening the entire coding region, 5′UTR and 3′UTR of MSY2 in 326 infertile patients with oligospermia/azoospermia and 210 controls. They were as follows: c.26T>G, c.187T>C, c.239C>A, c.271+22G>A, c.272-8C>T, c.335+144A>G, c.745-58T>C, and c.1095+16A>G, according to the nomenclature recommendations of sequence variations (http://www.hgvs.org/mutnomen). Of these, c.26T>G, c.187T>C, c.745-58T>C, and

Comment

To investigate the genetic causes of idiopathic human male infertility, mutation screening of candidate genes in patients with spermatogenic impairment is a direct and effective approach. In addition to gene mutation, other genetic variations, such as SNPs, have also been reported to be able to influence the susceptibility to impaired spermatogenesis.²¹

In the present study, we performed not only mutation screening of the MSY2, but also an analysis of its association with idiopathic male

Conclusions

The results of our study suggest that some polymorphisms of MSY2 might be associated with impaired spermatogenesis and provide evidence that the gene might be involved in modifying the susceptibility to idiopathic male infertility in humans. To confirm this and to further elucidate its mechanisms, more in-depth studies on more populations with functional analysis are needed.

Acknowledgments

Authors Y.D. and W.Z. contributed equally to this work.

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The underlying pathophysiology which results in male factor infertility is often multifactorial and complex. While it can be difficult to determine an exact cause of infertility in men, associations between genetics, epigenetics, and infertility may provide important explanations for reproductive dysfunction. Since greater than 2000 genes are involved in spermatogenesis, it is not surprising that genetic factors appear to contribute greatly to proper reproductive function. Men with azoospermia possess the highest frequency of genetic aberrations, but the number of identified genetic anomalies contributing to less severe defects in spermatogenesis is ever expanding. In addition to genetics, variations in the epigenetic landscape may confer a predisposition to infertility, result in perturbations in semen analysis parameters, or lead to diminished outcomes with assisted reproductive technology. Ongoing research is being conducted to delineate clear mechanistic pathways which may impact clinical outcomes and treatment options in the future.
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: This work was supported by the National Natural Science Foundation of China (grant 30470960) and the China Medical Board Foundation of New York.

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InfertilitySome Single Nucleotide Polymorphisms of MSY2 Gene Might Contribute to Susceptibility to Spermatogenic Impairment in Idiopathic Infertile Men

Objectives

Methods

Results

Conclusions

Section snippets

Study Participants

Results

Comment

Conclusions

Acknowledgments

Lancet

J Biol Chem

Mol Cell Endocrinol

Eur J Cancer

Genetic dissection of mammalian fertility pathway

Nat Med

Molecular genetics of human male infertility: from genes to new therapeutic perspective

Curr Pharm Des

Knockout mice provide novel insights into meiotic chromosome and telomere dynamics

Cytogenet Genome Res

Specific arrests of spermatogenesis in genetically modified and mutant mice

Cytogenet Genome Res

The making of a spermatozoon: a molecular perspective

Dev Genet

Transcriptional regulatory strategies in male germ cells

J Androl

The Y-box factors: a family of nucleic acid binding proteins conserved from Escherichia coli to man

New Biol

Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteins

Bioessays

Infertility
Some Single Nucleotide Polymorphisms of MSY2 Gene Might Contribute to Susceptibility to Spermatogenic Impairment in Idiopathic Infertile Men