Idiopathic male infertility in the Han population in China is affected by polymorphism in the VDAC2 gene

Abstract

BackgroundIt has been proved that human voltage-dependent anion channel 2 (VDAC2) plays a significant role in sperm function and male fertility. This study was primarily aimed at exploring whether VDAC2 is a risk factor for idiopathic male infertility.ResultsWe determined a significantly increased risk of idiopathic infertility with abnormal semen parameters in association with the variant rs2804535 and a decreased risk of idiopathic infertility with abnormal semen parameters in association with the variant rs11001334. However, among subjects with normal semen parameters, no significant differences could be found in these genotypes. Moreover, we could not find any differences in the variants rs7896741 and rs1259503, which showed no risk of male infertility, whether normal or abnormal.Materials and methodsAll of the experimental subjects, including 523 men who cannot conceive children and 277 fertile controls, underwent complete historical and physical examinations. Each participant donated an ejaculate for semen analysis and 5 ml of peripheral blood for genomic DNA extraction. A computer-assisted semen analysis system was used for the semen analysis. Four single-nucleotide polymorphisms were identified and analyzed using TaqMan SNP Genotyping Assays.ConclusionsThe result shows that the relationships between different variants in the VDAC2 gene and male fertility differ, and the individuals who carry those variants may have a decreased or increased risk of abnormal semen parameters associated with male infertility.

The impact of antisperm antibodies on human male reproductive function: an update

“…Another hypothetic risk factor associated with a deleterious impact on the structure of the BTB is testicular sperm extraction (TESE) procedure, a common technique used for testicular sperm retrieval in cases of non-obstructive azoospermia (NOA), and several were the studies that focused on this aspect. Surprisingly, in terms of ASA development, only two studies were published, both concluding that TESE procedure does not lead to a significant increase of serum ASA levels (Komori et al 2004, Ozturk et al 2011. Children testicular rupture, a rare complication of testicular trauma, in which surgery is recommended due to the extrusion of the testicular contents, was also studied in the context of ASA production.…”

“…Additionally, another study led to the identification of two human sperm proteins, which are simultaneously recognized by recombinant human zona pellucida (rhZP) glycoproteins and by ASA eluted from infertile ASA patients (Petit et al 2013). Specifically, the glutathione S-transferase M3 (GSTM) involved in detoxification processes and crucial to sperm as it prevents sperm membrane lipid peroxidation, through ROS elimination via glutathione (Hemachand & Shaha 2003), and the ionic channel, voltage-dependent anion-selective channel 2 (VDAC2), known to participate in energy production since it transports adenine nucleotides, Ca 2+ , and other metabolites at the level of the outer mitochondrial membrane (Petit et al 2013), and already associated with male infertility (Pan et al 2016.…”

Is the Secret of VDAC Isoforms in Their Gene Regulation? Characterization of Human VDAC Genes Expression Profile, Promoter Activity, and Transcriptional Regulators

“…A peculiar expression of VDAC isoforms was observed in cells and tissues of the germinal lines of different organisms. While VDAC1 is mainly located in cells of reproductive organs necessary to support the development of gametes [ 24 , 25 ], VDAC2 and VDAC3 are expressed in a specific portion of sperm and oocyte, and genetic variants or the aberrant regulation of these genes are correlated with infertility [ 26 , 27 ].…”

The secret of VDAC isoforms is in their gene regulation? Characterization of human VDAC genes expression profile, promoter activity, and transcriptional regulators

“…A peculiar expression of VDAC isoforms was observed in cells and tissue of the germinal lines of different organisms. While VDAC1 is mainly located in cells of reproductive organs necessary to support the development of gametes [24, 25], VDAC2 and VDAC3 are expressed in a specific portion of sperm and oocyte and genetic variants or the aberrant regulation of these genes are correlated with infertility [26, 27].…”