Interaction of thyroid hormonal imbalance, obesity, and Y-chromosomal gene dysregulation in male infertility: a case–control study

OBJECTIVES: This study aimed to investigate the association between thyroid hormone disturbances, obesity-related parameters, and the expression profiles of Y-linked spermatogenic genes (AZFa, AZFb, and AZFc) in infertile men, and to determine whether endocrine and metabolic alterations predict AZF gene dysregulation. METHODS: A case-control study included 150 infertile men and 150 fertile controls. Anthropometric indices and hormonal, biochemical, and inflammatory markers were assessed. Relative expression levels of AZFa, AZFb, and AZFc genes were quantified using qRT-PCR and the 2ˆ-ΔΔCT method. Correlation analysis, LASSO regression, and ROC curve modeling were performed to identify predictors of AZF gene downregulation. RESULTS: Infertile men had significantly higher BMI, waist circumference, and thyroid-stimulating hormone (TSH) levels, with reduced triiodothyronine (T3) and thyroxine (T4) concentrations (p<0.001). AZFa, AZFb, and AZFc expression levels were significantly decreased and negatively correlated with TSH, BMI, and inflammatory cytokines. A combined model of TSH, BMI, and interleukin-6 demonstrated the highest diagnostic accuracy (AUC=0.88), with 86 % sensitivity and 80 % specificity. CONCLUSIONS: Thyroid dysfunction, obesity, and systemic inflammation synergistically downregulate AZF gene expression and impair spermatogenesis. Integrating endocrine, metabolic, inflammatory, and molecular markers may improve diagnostic precision and personalized management of male infertility.