The Role of the Hydrogen Sulfide Pathway in Male and Female Urogenital System in Health and Disease

Significance: The endogenous hydrogen sulfide (H₂S) pathway produces an array of biological effects that vary depending on the bodily region. In addition, the H₂S pathway's relevance often changes depending on a healthy or disease state. There is abundant evidence pointing to a key role for this pathway in male and female genito-urinary diseases, suggesting it as a possible target for new therapeutic approaches. Recent Advances: The tissue-specific localization of the H₂S Enzymes in the genito-urinary tract has allowed for a better understanding of its role in the body's pathophysiology. Indeed, in humans, cystathionine-γ-lyase (CSE) plays a major role in corpus cavernosum whereas cystathionine-β-synthase (CBS) plays a role in bladder functioning. The prostate epithelium expresses CBS and CSE, but stromal CSE only. In the uterus, up- or downregulation of CBS and CSE varies strongly depending on the female's hormonal cycle or pregnancy.

Critical issues: There is still the need to better define the male and female's sexual hormonal roles in regulating the H₂S pathway, particularly in human pathological conditions. The lack of a correlation between human and animal data should be carefully considered when planning preclinical studies. The unmet need for selective enzymatic inhibitors and the different methodologies for H₂S measurements still represent a critical issue in this research field.

Future directions: It is feasible that the L-cysteine/H₂S pathway can represent an alternative therapeutic target in genito-urinary tract disorders. The research should focus on erectile dysfunction and preeclampsia, characterized by vascular defect, as well as on bladder disorders where the urothelium is compromised. Antioxid. Redox Signal. 27, 654-668.

bladder; corpus cavernosum; female; hydrogen sulfide; male; uterus.