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

Created February 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

* Hypothesis - Autism can be different between twins due to HPV differences in placenta – Nov 2017 * Autism 4 times more likely if low vitamin D during first trimester – Oct 2016 * Autistic child 2.4 X more likely if less than 10 ng of vitamin D during 2nd trimester – April 2017 * Herpes virus infection while pregnant increases Autism risk by 2 X (Vitamin D not mentioned) – Feb 2017 * Autism rate in siblings reduced 4X by vitamin D: 5,000 IU during pregnancy, 1,000 IU to infants – Feb 2016 * Overview Autism and vitamin D

Highlights

  • 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.

Tags: Autism Pregnancy