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

• Published in: The Journal of steroid biochemistry and molecular biology 2018-06, Vol.180, p.73-80
• Main Authors: Ali, Asad, Cui, Xiaoying, Alexander, Suzanne, Eyles, Darryl
• Format: Article
• Language: English
• Subjects: Animals; Autism; Cytokines; Cytokines - metabolism; Developmental Disabilities - etiology; Developmental Disabilities - pathology; Disease Models, Animal; DVD-deficiency; Epidemiology; Female; Fetuses; IL-1β; IL-6; Immune response; Immune status; Inflammation; Interleukin 6; Lipopolysaccharides; Male; Placenta; Placenta - drug effects; Placenta - immunology; Poly I-C - toxicity; Poly(I:C); Polyinosinic:polycytidylic acid; Pregnancy; Rats; Rats, Sprague-Dawley; Vitamin D; Vitamin D Deficiency - chemically induced; Vitamin D Deficiency - complications; Vitamin deficiency
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2018.01.015

•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. 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.