Evaluation of Lead exposure's link to autism-like behavior and Shank 3 gene expression in C57BL/6J mice.

Autism spectrum disorder (ASD) affects about 1 in 100 people worldwide, yet its causes remain poorly understood. Environmental factors, such as perinatal lead (Pb) exposure, have been linked to neurodevelopmental disruption, especially during periods when the blood-brain barrier is immature. This study aimed to assess ASD-like behavioral outcomes in offspring following maternal Pb exposure during neurodevelopment using a C57BL/6J mouse model. Pregnant dams received 100 ppm Pb acetate in their drinking water from the second week of gestation until weaning; controls were given deionised distilled water. Male offspring underwent behavioral assessments at 5 and 9 weeks of age using the three-chambered Social-Nonsocial (S-NS) interaction test and the Morris water maze. Pb concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), and real-time PCR was used to target Shank3, an ASD-associated gene. Lead concentrations were significantly elevated in the blood, brain, bone, liver, and kidney of exposed offspring, confirming effective maternal-foetal Pb transfer. However, no significant differences were observed between groups in behavioral performance or Shank3 expression. These findings suggest that perinatal Pb exposure at 100 ppm in the last trimester of pregnancy, under the conditions tested, does not induce measurable ASD-like phenotypes in male C57BL/6J mice. Further studies are warranted to investigate dose-dependent effects, sex-specific vulnerabilities, and the broader molecular pathways involved.