The placental immune response is dysregulated developmentally vitamin D deficient rats: Relevance to autism

Abstract

Emerging evidence suggests that maternal or developmental vitamin D (DVD) deficiency is a risk factor for Autism Spectrum Disorders. A well-established association has also been found between gestational infection and increased incidence of autism. Placenta mediates the maternal immune response in respect to the foetus. The placenta is also a major source of vitamin D and locally produced vitamin D is an essential regulator of immune function during pregnancy. Here we investigate the effects of DVD-deficiency on baseline placental immune status and in response to the well-known viral and bacterial immune activating agents polyriboinosinic-polyribocytidylic acid (poly(I:C) and lipopolysaccharide (LPS). We show DVD-deficiency does not affect baseline inflammatory cytokines in placenta. However, when challenged with poly(I:C) but not LPS, DVD-deficient placentas from male foetuses had higher production of IL-6 and 1L-1β compared to control placentas. This suggests the developing DVD-deficient male foetus may be particularly vulnerable to maternal viral exposures. This in turn may have adverse implications for the developing male brain. In conclusion, a dysregulated placental immune response may provide a plausible mechanism for both the epidemiological links between DVD-deficiency and increased male incidence of developmental conditions such as autism.

Keywords: Autism; DVD-deficiency; IL-1β; IL-6; Placenta; Poly(I:C); Vitamin D.