Dose-dependent effect of curcumin nanomicelle on autophagy signaling in testis; a study on normal Wistar rats.

BACKGROUND

Curcumin nanomicelles (CNM), a bioavailable formulation of curcumin, have demonstrated therapeutic potential due to their antioxidant and anti-inflammatory properties. However, increasing evidence indicates that dose, exposure duration, and physiological context may influence their biological effects in reproductive tissues. This study investigated the dose-dependent impact of CNM on testicular histology, carbohydrate and lipid storage patterns, apoptosis, testosterone status, and autophagy-related gene expression in healthy rats.

METHODS AND

RESULTS

Adult male rats were orally administered CNM at doses of 7.5, 15, or 30 mg/kg for 48 days. Histomorphometric analyses revealed significant reductions in the number of Leydig and Sertoli cells, germinal epithelium height, seminiferous tubule diameter, and the percentage of tubules with positive spermatogenic indices (TDI and SPI) in the 15 and 30 mg/kg groups. Histochemical staining showed a dose-dependent reduction in PAS-positive carbohydrate-associated reactivity and an increase in SBB-positive lipid-associated staining in germ and somatic cells. These findings indicate altered carbohydrate and lipid storage patterns but do not directly measure metabolic flux or pathway activity. CNM also reduced serum testosterone levels and ANS-positive Leydig cell fluorescence, an indirect histochemical indicator of lipid-associated steroidogenic potential, while increasing TUNEL-positive apoptotic cells, particularly at higher doses. In addition, CNM administration upregulated the mRNA expression of autophagy-related genes (Atg7, Beclin-1, p62, and LC3-I) in whole testicular tissue. These transcript-level findings suggest modulation of autophagy-associated signaling but do not by themselves establish autophagic flux or cell-specific autophagic activity.

CONCLUSIONS

These findings suggest that CNM alters testicular structural organization, carbohydrate and lipid storage patterns, testosterone status, apoptosis, and autophagy-related gene expression in a dose-dependent manner. The conclusions have been revised to reflect the measured endpoints and to avoid unsupported claims regarding steroidogenic activity, metabolic pathway flux, autophagic activity, or cell-specific autophagy mechanisms.