Background: Phthalates are endocrine-disrupting chemicals associated
with reproductive toxicity. Aim: This study provides a comparative
evaluation of the effects of dibutyl phthalate (DBP) and di-(2-ethylhexyl)
phthalate (DEHP) on testicular injury in immature mice. Methods: Fortyeight
21-day-old Swiss albino male mice were allocated into eight groups:
control, corn oil vehicle, and DBP- or DEHP-treated groups receiving 100,
200, or 400 mg/kg body weight by oral gavage for 10 consecutive days.
Histological evaluation followed 7 and 10 days of exposure (postnatal days
28 and 31). Results: Both DBP and DEHP induced testicular injury,
including germ cell disorganization, cytoplasmic vacuolization, germ cell
loss, and multinucleated giant cell (MGC) formation. Morphometric
analysis demonstrated a significant reduction in seminiferous tubule
diameter in both treatment groups, with a greater decrease in DEHPexposed
animals at both time points. DBP-treated groups exhibited a high
incidence of MGCs, reaching 93.11% and 84.50% at 28 and 31 days,
respectively. In contrast, DEHP-treated groups showed a lower incidence of
MGCs, reaching 56.17% at 28 days, with complete absence at 31 days
despite more severe degeneration and germ cell depletion. Two distinct
MGC types were identified: a dark eosinophilic type with dense cytoplasm
and relatively regular nuclei, and a pale foamy type with vacuolated
cytoplasm and irregular condensed nuclei, suggesting germ cell symplasts
and macrophage-derived giant cells, respectively. Conclusion: Both DBP
and DEHP induced MGC formation, but their progression differed, with
prolonged MGC occurrence after DBP exposure and more severe germ cell
loss following DEHP exposure. Further mechanistic studies are warranted.