Kefir Mitigates Testicular Histopathological and Immunohistochemical Alterations Induced by High-fructose Corn Syrup in Juvenile Wistar Rats.

High-fructose corn syrup (HFCS) consumption has been increasingly associated with reproductive dysfunction, yet the potential protective role of natural probiotic products such as kefir remains insufficiently explored. This study investigated the effects of kefir supplementation on HFCS-induced testicular damage in juvenile male Wistar rats. Twenty-four four-week-old rats (≈ 100 g) were maintained under controlled environmental conditions and randomly assigned to four groups: Control, Kefir, HFCS, and HFCS+Kefir. Kefir was administered by gastric gavage at 1 mL/100 g body weight daily, while HFCS-55 was provided ad libitum in drinking water (20%, w/v) for eight weeks. At the end of treatment, rats were anesthetized, and testicular tissues were collected for biochemical, histological, and immunohistochemical analyses. HFCS exposure markedly increased apoptotic and inflammatory markers, including p53, Caspase-3, Bax, TNF-α, and Nf-κB, while reducing the antiapoptotic marker Bcl-2. IGF-1Rα expression, seminiferous tubule diameters, and Johnsen's scores were also significantly impaired, accompanied by a pronounced rise in TUNEL-positive cells. Kefir supplementation substantially ameliorated HFCS-induced alterations, reflected by decreased apoptotic and inflammatory marker expression, improved histological architecture, and partial restoration of spermatogenic activity. These findings suggest that kefir mitigates HFCS-induced testicular injury through its antiapoptotic and anti-inflammatory effects. Kefir may therefore serve as a beneficial dietary supplement for protecting male reproductive health against fructose-related metabolic stress.