Investigation of testicular METRNL and RARRES2 expression in non-obstructive azoospermia

Non-obstructive azoospermia is a severe form of male infertility characterized by impaired spermatogenesis. Given the strong evidence linking obesity and chronic inflammation to male reproductive dysfunction, we aimed to investigate the role of adipokines METRNL (Meteorin-like protein) and RARRES2 (Chemerin) in non-obstructive azoospermia pathogenesis. We conducted a retrospective study using the testicular biopsy samples of 35 patients (12 cases were obese, 23 cases had normal body mass index) with non-obstructive azoospermia and 18 patients with obstructive azoospermia and/or vas deferens agenesis. We compared the testicular METRNL and RARRES2 mRNA expressions of obese and non-obese non-obstructive azoospermia cases with controls (obstructive azoospermia cases with intact spermatogenesis). We detected significantly increased RARRES2 expression in both obese and non-obese non-obstructive azoospermia patients. Even though statistically non-significant, we observed a higher RARRES2 expression trend in histologically more severe non-obstructive azoospermia cases. We also detected a significant inverse correlation between RARRES2 expression and Johnsen score, an indicator of seminiferous tubule integrity and spermatogenesis status. Conversely, we found no significant difference in METRNL expression across the study groups. Broader studies are needed to validate our results and investigate the mechanisms of increased RARRES2 (chemerin) expression in the azoospermia cases with defective spermatogenesis.