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Hypothesis: male autism risk increased if placental virus and low vitamin D – Feb 2018

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

The Journal of Steroid Biochemistry and Molecular Biology, online 3 Feb 2018, https://doi.org/10.1016/j.jsbmb.2018.01.015
Asad Alia, Xiaoying Cuia, Suzanne Alexandera, b, Darryl Eylesa, b


  • Developmental Vitamin D deficiency alters placental inflammatory response.
  • Developmental Vitamin D deficient placentas containing a male foetus are selectively vulnerable to exposure to viral particles.
  • Variability in placental inflammatory response may inform future mechanisms for the links between DVD-deficiency and autism and the extreme male brain theories of autism.

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.

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