This review considers a link between prematurity and autism by comparing symptoms, physiological abnormalities, and behavior. It focuses on the bidirectional signaling between the microbiota and the brain, here defined as the microbiota-gut-vagus-heart-brain (MGVHB) axis and its systemic disruption accompanying altered neurodevelopment. Data derived from clinical and animal studies document increased prevalence of gastrointestinal, cardiovascular, cognitive, and behavioral symptoms in both premature and autistic children and suggest an incomplete maturation of the gut-blood barrier resulting in a "leaky gut," dysbiosis, abnormalities in vagal regulation of the heart, altered development of specific brain regions, and behavior. Furthermore, this review posits the hypothesis that common genetic variants link the abnormalities in the MGVHB axis in premature and autistic pathologies. This hypothesis is based on the recently identified common genetic variants: early B cell factor 1 (EBF1), selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC), and angiotensin II receptor type 2 (AGTR2), in the maternal and infant DNA samples, associated with risk of preterm birth and independently implicated in a risk of autism. We predict that the AGTR2 variants involved in the brain maturation and oxytocin-arginine-vasopressin (OXT-AVP) pathways, related to social behavior, will contribute to our understanding of the link between prematurity and autism paving a way to new therapies.

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IntroductionDepression during pregnancy and lactation is a significant clinical problem that affects 7% to 19% of women. Often the depression develops early during the first trimester of pregnancy, during the fetal cardiovascular system development and is associated with increased levels of circulating cortisol that passes through the blood‐placenta barrier. ln turn, the increased cortisol inhibits the apelin synthesis and the apelinergic system activity that is essential for cardiogenesis and angiogenesis during the embryonic and fetal development.PurposeThe main aim of the project is to investigate the effect of apelinergic system on the development of the cardiovascular system in the offspring of female Sprague Dawley rats (SD) with depressive‐like behaviour.MethodsThe research was carried out on 14 rat dams and their offspring of both sexes. Half of the dams underwent chronic immobilization stress to induce depression, the other dams were not stressed. The development of depression in dams was confirmed by a self‐care test and urinary corticosterone concentration. P28 weaned offspring underwent ECHO examination. Following the euthanasia. their hearts were removed for morphological, biochemical, and Real‐Time PCR analysis. Consent was obtained from The Local Animal Research Ethics Committee (031/2016).ResultsHeart morphology was normal and the left and right ventricle function were comparable in the offspring of both control and stressed dams. However, the offspring of stressed dams had a significantly higher left ventricular weight and increased heart rate, while the aortic diameter was lower in these rats compared to the offspring of control dams. Expression of BNP mRNA was significantly higher in the offspring of stressed compared to the offspring of control dams. Glucocorticoid receptor mRNA expression was significantly higher in the offspring of stressed compared to the offspring of control dams. On the other hand the apelin mRNA expression was significantly lower in the offspring of stressed than control dams, whereas the APJ mRNA expression was significantly higher in the offspring of stressed dams.ConclusionOur results indicate that maternal depression during pregnancy and lactation is associated with developmental cardiovascular abnormalities and lower apelinergic system activity. These observations support an important role of apelinergic system in the cardiovascular remodeling of the developing heart in response to maternal depression.Support or Funding InformationThis research was supported by the Medical University of Warsaw, Young Researcher's Grant (1MA/PM2/18).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.