Subchronic exposure to an abamectin–chlorantraniliprole mixture alters mammary gland integrity, cell proliferation and apoptosis, lactation, and reproductive performance in female rabbits

This study investigated the effects of subchronic exposure to Voliam Targo® (VT), a binary insecticide containing abamectin and chlorantraniliprole, on maternal reproduction, lactation, lipid metabolism, milk composition, and mammary gland integrity in female rabbits. Thirty nulliparous rabbits (30 females and 30 males; Oryctolagus cuniculus) were randomly assigned to control or VT-treated groups (15 mg/kg body weight/day by oral gavage) for 12 consecutive weeks. Following a 17-day pre-mating period, animals underwent artificial insemination using heterospermic or homospermic matings, with treatment maintained throughout gestation and lactation until postnatal day 35. Mammary gland alterations were evaluated using biochemical, histopathological, histomorphometric, and immunohistochemical analyses. VT exposure significantly increased maternal body weight during gestation and lactation while reducing mammary gland weight. Reproductive performance varied according to mating pattern, with paternal-only exposure increasing litter size, whereas biparental exposure produced the smallest litters and the highest maternal body weight during lactation. Early lactation was characterized by a transient increase in milk yield accompanied by decreased fat content and increased dry matter, protein, lactose, and pH. Lipid profiling demonstrated persistent hypercholesterolemia, intermittent hypertriglyceridemia, and progressive high density lipoprotein (HDL) elevation. Histopathological examination revealed acinar epithelial necrosis, inflammatory infiltration, fibrosis, ductal ectasia, and vascular congestion. Histomorphometry confirmed enlargement of acinar structures and epithelial nuclei, reflecting hypertrophy and architectural disorganization. Immunohistochemistry demonstrated increased Ki-67, p53, and Bcl-2 expression, suggesting dysregulated cell proliferation and apoptosis. These findings demonstrate that subchronic VT exposure compromises mammary gland integrity, lipid homeostasis, lactational function, and reproductive performance, highlighting potential reproductive health risks associated with chronic insecticide exposure.