Mitochondrially encoded NADH dehydrogenase subunit 3 (MT-ND3) gene variants in asthenozoospermia-associated male infertility

Variantes del gen de la subunidad 3 de la NADH deshidrogenasa (ND3) codificado mitocondrialmente en la infertilidad masculina asociada a astenozoospermia

Background: Male infertility is a complex, multifactorial condition contributing to approximately 50% of infertility cases. Among these, asthenozoospermia (reduced sperm motility) accounts for around 13% of male infertility cases. This study aims to investigate the mitochondrial ND3 gene variants in asthenozoospermic infertile men in Jordan. Methods: 188 semen samples (117 asthenozoospermic and 71 normozoospermic) were collected from the in-vitro fertilization (IVF) unit at the Jordanian Royal Medical Services. Mitochondrial DNA (mtDNA) was extracted and amplified, and the Mitochondrially encoded NADH dehydrogenase subunit 3 (MT-ND3) gene was sequenced, followed by the identification of genetic variants. Results: Seventeen single-nucleotide polymorphisms (SNPs) were detected in the MT-ND3 gene in the examined samples. One novel synonymous variant (m.10313 A>T) was identified exclusively in the normozoospermic group, while the remaining variants were previously reported in the National Center for Biotechnology Information (NCBI) databases. Six missense variants were found: two in the asthenozoospermic group (rs41487950 T>C (Ile9Thr) and rs1603222800 G>A (Ala103Thr)), three in the normozoospermic group (rs202131419 G>A (Gly29Ser), rs193302928 T>C (Val88Ala), and rs1603222776 T>C (Met89Thr)), and one common variant (rs2853826 A>G (Thr114Ser)) in both groups. Additionally, eleven synonymous variants were identified in the study population. Conclusions: Although no statistically significant associations were found between the identified MT-ND3 gene SNPs and asthenozoospermia, several detected variants in asthenozoospermic samples are predicted to alter the protein’s structure. Sample size is a limitation of the current study; therefore, further investigations are required to assess the potential impact of these variants on male infertility across diverse populations.

Resumen

Antecedentes: La infertilidad masculina es una afección compleja y multifactorial que contribuye a aproximadamente el 50% de los casos de infertilidad. Entre estos, la astenozoospermia (reducción de la movilidad espermática) representa alrededor del 13% de los casos de infertilidad masculina. Este estudio tiene como objetivo investigar las variantes mitocondriales del gen ND3 en hombres infértiles astenozoospérmicos en Jordania. Métodos: Se obtuvieron 188 muestras de semen (117 astenozoospérmicos y 71 normozoospérmicos) de unidades de (la Unidad de Fertilización In Vitro) FIV de los Servicios Médicos Reales de Jordania. Se extrajo y amplificó el ADN mitocondrial (ADNmt), se secuenció el gen (Gen del gen de la subunidad 3 de la NADH deshidrogenasa codificado mitocondrialmente) MT-ND3 y se identificaron las variantes genéticas. Resultados: Se detectaron diecisiete polimorfismos de un solo nucleótido (SNP) en el gen MT-ND3 en las muestras examinadas. Se identificó una nueva variante sinónima (m.10313 A>T) exclusivamente en el grupo normozoospérmico, mientras que las variantes restantes se habían reportado previamente en las bases de datos del Centro Nacional para la Información Biotecnológica (NCBI). Se encontraron seis variantes sin sentido: dos en el grupo astenozoospérmico (rs41487950 T>C (Ile9Thr) y rs1603222800 G>A (Ala103Thr)), tres en el grupo normozoospérmico (rs202131419 G>A (Gly29Ser), rs193302928 T>C (Val88Ala) y rs1603222776 T>C (Met89Thr)), y una variante común (rs2853826 A>G (Thr114Ser)) en ambos grupos. Además, se identificaron once variantes sinónimas en la población del estudio. Conclusiones: Aunque no se encontraron asociaciones estadísticamente significativas entre los SNP identificados del gen ND3 y la astenozoospermia, se predice que varias variantes detectadas en muestras astenozoospérmicas alteran la estructura de la proteína. El tamaño de la muestra es una limitación del presente estudio; por lo tanto, se requieren más investigaciones para evaluar el posible impacto de estas variantes en la infertilidad masculina en diversas poblaciones.

mtDNA; Asthenozoospermia; Sperm motility; MT-ND3 gene

Palabras Clave

ADNmt; Astenozoospermia; Motilidad espermática; Gen MT-ND3

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