Vitamin D Supplementation after Orchiopexy Promotes Testicular Recovery via an Attenuated cGAS-STING Pathway to Reduce Pyroptosis

Background: Cryptorchidism has gradually become one of the common congenital malformations of the urinary system. In this study, we explored the influence of vitamin D (VD) on testicular recovery after cryptorchidism and elucidated the underlying mechanism. Methods: The correlation between 25-(OH) (oxhydryl) VD levels and postoperative testicular volume in 30 children undergoing cryptorchidism surgery was analyzed retrospectively. Thirty 20-day-old cryptorchidism SD (Sprague-Dawley) rats were divided into cryptorchidism (group A, sacrificed when diagnosed), postoperative (group B, sacrificed 20 days after orchiopexy with normal feeding), and VD groups (group C, sacrificed after orchiopexy with VD feeding). Ten 20-day-old SD rats were used as the control group. The protein expression levels of Caspase-1, IL-1 beta (interleukin-1 beta), and NLRP3 (NOD-like receptor thermal protein domain associated protein 3) were determined using western blotting, and cGAS and STING mRNA levels were determined using real-time PCR (polymerase chain reaction). Results: Testicular size after cryptorchidism positively correlated with body 25-(OH) VD levels. The weights of the testis and epididymis were the highest in group C. The expression levels of pyroptosis-related proteins (NLRP3, IL-1 beta, and caspase-1) in the testes were lower in group C than those in groups A and B. The expression levels of cGAS (cyclic guanosine monophosphateadenosine monophosphate synthase), and STING (stimulator of interferon genes) in testicular tissues were the highest in group A and comparable in groups B and C. Conclusions: Cryptorchidism surgery combined with VD can promote rapid testicular recovery. VD supplementation reduces pyrogenesis, modulates the cGAS-STING signaling pathway, and promotes testicular recovery after cryptorchidism surgery.