Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress.

Fetal hypoxia is a common complication of pregnancy. It has been shown to programme cardiac and endothelial dysfunction in the offspring in adult life. However, the mechanisms via which this occurs remain elusive, precluding the identification of potential therapy. Using an integrative approach at the isolated organ, cellular and molecular levels, we tested the hypothesis that oxidative stress in the fetal heart and vasculature underlies the molecular basis via which prenatal hypoxia programmes cardiovascular dysfunction in later life. In a longitudinal study, the effects of maternal treatment of hypoxic (13% O(2)) pregnancy with an antioxidant on the cardiovascular system of the offspring at the end of gestation and at adulthood were studied. On day 6 of pregnancy, rats (n = 20 per group) were exposed to normoxia or hypoxia ± vitamin C. At gestational day 20, tissues were collected from 1 male fetus per litter per group (n = 10). The remaining 10 litters per group were allowed to deliver. At 4 months, tissues from 1 male adult offspring per litter per group were either perfusion fixed, frozen, or dissected for isolated organ preparations. In the fetus, hypoxic pregnancy promoted aortic thickening with enhanced nitrotyrosine staining and an increase in cardiac HSP70 expression. By adulthood, offspring of hypoxic pregnancy had markedly impaired NO-dependent relaxation in femoral resistance arteries, and increased myocardial contractility with sympathetic dominance. Maternal vitamin C prevented these effects in fetal and adult offspring of hypoxic pregnancy. The data offer insight to mechanism and thereby possible targets for intervention against developmental origins of cardiac and peripheral vascular dysfunction in offspring of risky pregnancy

Size constancy is preserved but afterimages are prolonged in typical individuals with higher degrees of self-reported autistic traits

Deficits in perceptual constancies from early infancy have been proposed to contribute to autism and exacerbate its symptoms (Hellendoorn et al., Frontiers in Psychology 6:1–16, 2015). Here, we examined size constancy in adults from the general population (N = 106) with different levels of self-reported autistic traits using an approach based on negative afterimages. The afterimage strength, as indexed by duration and vividness, was also quantified. In opposition to the Hellendoorn and colleagues’ model, we were unable to demonstrate any kind of relationship between abilities in size constancy and autistic traits. However, our results demonstrated that individuals with higher degrees of autistic traits experienced more persistent afterimages. We discuss possible retinal and post-retinal explanations for prolonged afterimages in people with higher levels of autistic traits

Cardiac function in adulthood.

<p>Values are mean±S.E.M. for the dP/dt max <i>a</i>, the heart rate-pressure product (RPP) <i>b</i>; and the heart rate responses to 10–6 M Carbachol <i>c</i> and to 10–7 M Isoprenaline <i>d</i>. Groups are: Normoxia, n = 6 (N,□), Hypoxia, n = 6 (H, ▪), Hypoxia+Vitamin C, n = 7 (HC, red histogram) and Normoxic+Vitamin C, n = 7 (NC, blue histogram). Significant (P<0.05) differences are: * vs. all, One-Way ANOVA with Tukey Test.</p

Fetal aorta and heart.

<p>Photomicrographs of individual examples of sections of the fetal aorta are shown in <i>a</i>. Bar scale is 100 µm. Values are mean±S.E.M. of the wall to lumen area ratio <i>b</i>; the density of nitrotyrosine staining in the aortic wall <i>c</i>, and the protein expression of HSP70 in the fetal heart <i>d</i>. Groups are: Normoxia, n = 8 (N,□), Hypoxia, n = 8 (H,▪), Hypoxia+Vitamin C, n = 8 (HC, red histogram) and Normoxic+Vitamin C, n = 8 (NC, blue histogram). Significant (P<0.05) differences are: * vs. all, † vs. H, One-Way ANOVA with Tukey Test.</p

Maternal and offspring data.

<p>Values are mean±S.E.M. for dams and offspring of Normoxic (N), Hypoxic (H), Hypoxic+Vitamin C (HC) and Normoxic+Vitamin C (NC) pregnancy. Placental weight, fetal haematocrit and fetal heart weight were taken at gestational day 20. Values for heart rate, left ventricular developed pressure (LVDP) and left ventricular end diastolic pressure (LVEDP) were taken from the isolated heart preparations. Significant (P<0.05) differences are:</p><p>*vs. normoxia, Mixed Linear Model for birth weight, placental weight, fetal absolute and relative heart weights; ANOVA+Tukey Test for all other variables.</p