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<p>Phthalates, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), are widely used plasticizers associated with male reproductive toxicity. This study evaluated the dose- and temporal-dependent effects of DBP and DEHP (100, 200, and 400&#xa0;mg/kg for 15 days) on testicular structure and function in immature Swiss albino mice at 36, 45, 50, and 70 days of age. Biochemical analyses revealed significant glutathione depletion accompanied by increased nitric oxide and lipid peroxidation levels, suggesting oxidative imbalance. Histological evaluation demonstrated severe dose-dependent testicular injury, particularly at 36–45 days, with the 400&#xa0;mg/kg groups showing 100% damaged seminiferous tubules and marked reductions in Johnsen’s scores (3.5 ± 0.17 vs. 9.9 ± 0.10 in controls). Increased Caspase-3 and NF-κB expression suggested possible involvement of apoptotic and inflammatory responses. Longitudinal assessment from 50 to 70 days revealed a dose-dependent recovery pattern, with substantial restoration in lower-dose groups, whereas higher doses remained associated with persistent tubular damage at 70 days (47.0% in DBP and 58.8% in DEHP groups). These findings suggest that the severity of testicular injury and the extent of recovery are influenced by phthalate exposure dose. Therefore, further studies are required to fully understand the underlying molecular mechanisms.</p>

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Phthalate induced testicular degeneration in mice: biochemical, histopathological and immunohistochemical evidence for the interplay of oxidative stress, caspase-3, and NF-κB signaling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Reda A. Ali,
  • Heba E. Aboulqasem,
  • Dalia Elzahraa F. Mostafa

摘要

Phthalates, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), are widely used plasticizers associated with male reproductive toxicity. This study evaluated the dose- and temporal-dependent effects of DBP and DEHP (100, 200, and 400 mg/kg for 15 days) on testicular structure and function in immature Swiss albino mice at 36, 45, 50, and 70 days of age. Biochemical analyses revealed significant glutathione depletion accompanied by increased nitric oxide and lipid peroxidation levels, suggesting oxidative imbalance. Histological evaluation demonstrated severe dose-dependent testicular injury, particularly at 36–45 days, with the 400 mg/kg groups showing 100% damaged seminiferous tubules and marked reductions in Johnsen’s scores (3.5 ± 0.17 vs. 9.9 ± 0.10 in controls). Increased Caspase-3 and NF-κB expression suggested possible involvement of apoptotic and inflammatory responses. Longitudinal assessment from 50 to 70 days revealed a dose-dependent recovery pattern, with substantial restoration in lower-dose groups, whereas higher doses remained associated with persistent tubular damage at 70 days (47.0% in DBP and 58.8% in DEHP groups). These findings suggest that the severity of testicular injury and the extent of recovery are influenced by phthalate exposure dose. Therefore, further studies are required to fully understand the underlying molecular mechanisms.