Nod-like receptor family pyrin domain-containing 3 inflammasome and its single-nucleotide polymorphisms in varicocele patients

Background Varicocele, characterized by abnormal dilation of the pampiniform venous plexus, is a leading cause of male infertility. Emerging evidence suggests that inflammation, particularly via activation of Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, may play a critical role in varicocele-associated testicular dysfunction. Objective To evaluate seminal NLRP3 inflammasome levels and NLRP3 rs10754558 gene polymorphism in varicocele patients, and assess their association with semen parameters and varicocele grades. Patients and methods This case–control study included 40 patients with varicocele and 40 age-matched healthy controls. Semen analysis assessed sperm concentration, motility, morphology, and leukocytospermia. Seminal NLRP3 levels were measured by enzyme-linked immunosorbent assay, and NLRP3 rs10754558 polymorphism was genotyped using PCR-restriction fragment length polymorphism. Results Varicocele patients showed significantly lower sperm concentration (44.9±43.9 vs. 53.2±21.3 million/ml, P =0.019) and motility (10.3±9.5 vs. 16.0±10.8%, P =0.014), and higher abnormal morphology (62.4±13.5 vs. 29.8±12.1%, P <0.001) than controls. Seminal NLRP3 levels were markedly elevated in varicocele patients (551.9±134.2 pg/ml) compared to controls (316.7±66.1 pg/ml, P <0.001), correlating positively with varicocele grade. The GG genotype of NLRP3 rs10754558 was more frequent in varicocele patients (35 vs. 12.5%, P =0.019), and was associated with worse semen parameters and higher seminal NLRP3 levels. Conclusion Elevated seminal NLRP3 levels and GG genotype of NLRP3 rs10754558 are associated with impaired semen quality and higher varicocele grades, indicating that NLRP3 inflammasome activation may contribute to varicocele pathophysiology and infertility risk.