Aflatoxin B1-Induced Teratogenic and Early Carcinogenic Alterations in Fetal Skin and Hair Follicles of Late-Gestation Mice

Background & Objective: Aflatoxin B1 (AFB1) is a potent hepatocarcinogen and teratogen with limited information regarding the effects of AFB1 on fetal skin development. This study examined the teratogenic and early pre-neoplastic effects of exposure to AFB1 during late gestation on fetal skin and hair follicles of mice.Materials & Methods: Thirty pregnant C57BL/6 mice were allocated to three groups: control (n=10), low-dose AFB1 (50 µg/kg, n=10) and high-dose AFB1 (100 µg/kg, n=10). AFB1 was given via oral gavage from E13 to E18 and fetuses were harvested at E19. Histopathology, immunohistochemistry (PCNA, p53, Ki-67 and caspase-3), quantitative PCR (Trp53, Bax, Bcl-2 and Cyp1a2), and Western-blot analysis for AFB1-DNA adducts were used to assess dorsal skin.Results: AFB1 resulted in a dose-dependent decrease in fetal weight and an increase in epidermal thickness (P<0.001), as well as epidermal hyperplasia, dysplastic changes and abnormalities of hair-follicles. Increased PCNA and Ki-67 labeling was noted, indicative of disturbed developmental proliferation, not definite neoplastic transformation. Nuclear p53 accumulation was seen in 78% of the high dose samples. There was an upregulation of Trp53 and Bax, a downregulation of Bcl-2, and AFB1-DNA adducts were found in 70% and 85% of the low and high dose fetuses, respectively.Conclusion: AFB1 can cause fetal growth restriction and developmental abnormalities of the skin and molecular changes that are indicative of genotoxic stress and early pre-neoplastic alteration in the fetus following exposure during late gestation. The key findings indicate the susceptibility of fetal skin to exposure from the mother to aflatoxin.