Genetic Determinants of Male Infertility: Insights from Molecular Biology
Keywords:
Male Infertility, Y-chromosome Microdeletions, AZF Region, Spermatogenesis Genes, TEX11, DMRT1, Oligozoospermia, and AzoospermiaAbstract
Male infertility is responsible for the loss of nearly half of all cases of infertility seen in clinical practice and occurs in about 7% of the world's male population. In this cross-sectional study, we analysed a set of genes relevant to both prevalence and clinical significance in 125 infertile men who attended reproductive medicine tertiary centres of excellence from January 2023 to December 2024. All participants were genetically screened: Y-chromosome microdeletion, karyotyping, and whole-exome sequencing of 78 known genes associated with spermatogenesis. The average age of the patients was 34.2 ± 5.8 years, and the mean duration of infertility was 3.7 ± 2.1 years. The mean sperm concentration was 8.4 ± 11.2 × 10⁶/mL, 38.4% of the subjects showed non-obstructive azoospermia, and 29.6% of the subjects showed severe oligozoospermia (<5 × 10⁶/mL). Sixty-seven patients (53.6%) had genetic abnormalities, with an 18.4% (AZFc), 20.8% (monogenic variants in the spermatogenesis genes), and 14.4% (chromosomal abnormalities) of these patients. In 15.2% of the oligozoospermic patients, abnormal methylation at the H19/IGF2 locus was found, whereas the published Normozoospermic controls showed an abnormal methylation in 8%.
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