The impact of maternal vitamin D deficiency during pregnancy and lactation on autism-like behavior in offspring.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments and stereotyped behaviors. Many epidemiological studies have found a potential relationship between vitamin D deficiency (VDD) and ASD. However, the mechanism remains unclear. In this study, a VDD model was established by feeding a vitamin D-depleted diet to 5-week-old female mice, from their adulthood through pregnancy to end of lactation. Social deficits, repetitive stereotyped behaviors and anxiety-like behaviors were evaluated in the offspring. The results showed the number of buried marbles was increased in the female offspring of the VDD group. Social defects were observed in both male and female offspring in the VDD group. Mechanistically, several markers of cell proliferation, such as Pcna and Ki67, were upregulated. And the number of TBR2+ cell, an intermediate progenitor cell, was increased in cerebral cortex of VDD-fed fetuses. Moreover, DKK1, a WNT/β-catenin pathway repressor, was elevated in cerebral cortex of VDD-fed fetuses. By contrast, β-catenin, a critical effector of the WNT/β-catenin pathway, was reduced in cerebral cortex of GD14 VDD fetuses. These results provide partial evidence that maternal vitamin D deficiency during pregnancy and lactation induces autism-like behaviors partly by suppressing WNT/β-catenin pathway in the cerebral cortex.