Ultrastructural testicular damage by water avoidance stress: therapeutic effects of nobiletin

We investigated the effects of nobiletin, an antioxidant, in rats with testicular damage induced by chronic water avoidance stress. Thirty male Sprague-Dawley rats were divided into five groups: Control; Nobiletin (NOB); Chronic Stress (CS); Chronic Stress+DMSO (CS+DMSO); and Chronic Stress+Nobiletin (CS+NOB). Healthy testicular morphology was seen in the Control and NOB groups. In the CS group, seminiferous tubule diameters and germinal epithelial thicknesses decreased, and basement membranes were thicker. This morphological damage was reduced in the CS+NOB group. Immunohistochemical analysis showed that anti-ZO-1 expression, which was intense in the Control and NOB groups, decreased in the CS group, and increased in CS+NOB, similar to Control and NOB. Electron microscopy indicated that the blood-testis barrier (BTB) maintained its integrity in the Control and NOB groups, lost its integrity in the CS group, and was largely preserved in CS+NOB. Biochemical analyses showed that oxidative stress markers, significantly increased in the CS group, decreased significantly in the CS+NOB group. These findings underscore the protective effect of NOB on the male reproductive system against chronic stress, suggesting that nobiletin might be a valuable supportive agent in the treatment of male infertility.