Placental Gene Expression and Maternal Allergic Asthma: Investigating Neurodevelopmental Pathways in a Mouse Model of Autism Spectrum Disorders
Date
2017-06-27
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Abstract
Recent epidemiological studies have suggested that mothers with onset allergies or asthma during pregnancy are at an increased risk for having a child with autism spectrum disorders (ASD). A novel mouse model of maternal allergic asthma (MAA) has shown ASD-like behavioral deficits in offspring of MAA dams in two genetically distinct mouse strains. However, the mechanisms underlying MAA remain unknown. One hypothesis is that induced allergic asthma may negatively impact the developing fetal brain by disrupting gene expression in the placenta. This study investigated alterations in gene expression in two distinct pathways critical for neurodevelopment in the placenta of MAA dams: the tryptophan (TRP) pathway and the long-chain polyunsaturated fatty acid (LC-PUFA) pathway. Specifically, C57Bl/6J (C57) and FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant (FVB) female mice, strains with distinct behavioral responses to MAA, were sensitized and exposed to ovalbumin during pregnancy on gestational day (G)9.5,12.5, and 17.5 and placentae were extracted on G17.5 four hours after the final OVA exposure. Placental RNA samples were analyzed for differences in expression of solute carrier family 7 member 5 (LAT1) and indoleamine 2,3-dioxygenase (Ido1) in the TRP pathway and fatty acid transport protein 4 (FATP4) and Acyl-CoA synthetase long-chain family member 3 (Acsl3) in the LC-PUFA pathway using quantitative reverse transcription PCR. Results reveal increased expression of Ido1 in C57 but not FVB MAA placentae, implicating strain-specific differences in TRP metabolism and its associated metabolic constituents, kynurenine and serotonin, as important mechanisms that may underlie the ASD-like behavioral deficits associated with MAA.
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Neuroscience, Autism spectrum disorders, Mouse model, Neurodevelopment, qRT-PCR, Placenta, Gene expression, Maternal allergic asthma