Antioxidant homeostasis is disturbed in fetuses with leptin-resistant genotypes: A cross-sectional study

Background: Leptin resistance is associated with lower reproductive efficiency, with deficiencies in embryo viability and growth leading to low prolificacy and high incidence of intrauterine growth restriction. Objective: We aimed to investigate the underlying mechanisms of the leptin-resistance, evaluating the antioxidant homeostasis of leptin-resistant and lean swine fetuses. Materials and Methods: The study included 70 plasma samples from fetuses at day 62 of gestation (mid-pregnancy), from breeds with (Iberian breed; n=35) and without leptin resistance (25% Large White x 25% Landrace x 50% Pietrain; n=35). The antioxidant status of the plasma samples was determined by photoinduced chemiluminescence whilst systemic oxidative stress was assessed determining plasma hydrogen peroxide concentration by enzimoimmunoassay. Results: Plasma total antioxidant capacity was significantly lower in leptin-resistant fetuses (p=0.003), whilst systemic oxidative stress was increased (p=0.02). Conclusion: Our results indicate key differences in the antioxidant status in pregnancies affected by leptin resistanc

La homeostatis antioxidante se altera en fetos con genotipo resistente a la leptina: un estudio transversal

La resistencia a la leptina se asocia con una menor eficiencia reproductiva, con deficiencias en la viabilidad y el crecimiento del embrión que conducen a una baja prolificidad y una alta incidencia de restricción del crecimiento intrauterinoLeptin resistance is associated with lower reproductive efficiency, with deficiencies in embryo viability and growth leading to low prolificacy and high incidence of intrauterine growth restriction

Polyphenols and IUGR pregnancies: Maternal hydroxytyrosol supplementation improves prenatal and early-postnatal growth and metabolism of the offspring.

Hydroxytyrosol is a polyphenol with antioxidant, metabolism-regulatory, anti-inflammatory and immuno-modulatory properties. The present study aimed to determine whether supplementing the maternal diet with hydroxytyrosol during pregnancy can improve pre- and early post-natal developmental patterns and metabolic traits of the offspring. Experiment was performed in Iberian sows fed a restricted diet in order to increase the risk of IUGR. Ten sows were treated daily with 1.5 mg of hydroxytyrosol per kg of feed between Day 35 of pregnancy (30% of total gestational period) until delivery whilst 10 animals were left untreated as controls. Number and weight of offspring were assessed at birth, on post-natal Day 15 and at weaning (25 days-old). At weaning, body composition and plasma indexes of glucose and lipids were measured. Treatment with hydroxytyrosol was associated with higher mean birth weight, lower incidence of piglets with low birth weight. Afterwards, during the lactation period, piglets in the treated group showed a higher body-weight than control piglets; such effects were even stronger in the most prolific litters. These results suggest that maternal supplementation with hydroxytyrosol may improve pre- and early post-natal development of offspring in pregnancies at risk of IUGR

Polyphenols and IUGR Pregnancies: Effects of Maternal Hydroxytyrosol Supplementation on Placental Gene Expression and Fetal Antioxidant Status, DNA-Methylation and Phenotype

The use of polyphenols is a promising strategy for preventing or alleviating intrauterine growth restriction (IUGR) because polyphenol supplementation increases plasma antioxidant capacity and improves oxidative stress at the feto-placental unit; which are recognized as main issues in IUGR. However, there is a scarcity of experimental data on both realistic benefits and potential hazards of polyphenol supplementation during gestation. Hence, we aimed to use a swine model of IUGR pregnancy to determine possible effects of maternal supplementation with polyphenols (hydroxytyrosol) on placental expression of genes involved in antioxidant homeostasis, vascularization and fetal growth and thus on antioxidant status, DNA-methylation and phenotypic traits (morphology and homeostasis) of the fetus. Hydroxytyrosol improves placental gene expression and fetal antioxidant status and glucose metabolism in a sex-dependent manner, in which males were favored in spite of developmental failures. Concomitantly, hydroxytyrosol prevented hypomethylation of DNA associated with oxidative stress. Finally, no major deleterious effects of hydroxytyrosol supplementation on constriction of the ductus arteriosus, a possible secondary effect of polyphenols during pregnancy, were found

Changes in ADWG (Kg/day ± S.E.M.) of piglets throughout lactation period.

<p>The panel A represents total differences between groups of treatment. Panels B, C and D represent between-treatments differences considering litter size (2–6, 7–8 and 9–10 piglets, respectively). Panels E and F represent within-treatment differences considering litter size in control and treated groups, respectively. Dark blue: Hydroxytyrosol group. Green: Control group. Red: 9–10 piglets/litter. Light blue: 8–7 piglets/litter. Black: 2–6 piglets/litter.</p

Indexes of glucose and lipid metabolism in piglets at weaning.

<p>Mean plasma concentrations (±SEM) of parameters related to lipid and glucose profile (mg/dl) for treatment (Hydroxytyrosol, HT, <i>vs</i>. Control group, C) and of litter size (2–6 <i>vs</i>. 7–10 piglets/litter).</p

Changes in body-weight (Kg/day) of piglets throughout the lactation period.

<p>The panel A represents total differences between groups of treatment. Panels B, C and D represent between-treatments differences considering litter size (2–6, 7–8 and 9–10 piglets, respectively). Panels E and F represent within-treatment differences considering litter size in control and treated groups, respectively. Dark blue: Hydroxytyrosol group. Green: Control group. Red: 9–10 piglets/litter. Light blue: 8–7 piglets/litter. Black: 2–6 piglets/litter.</p

Ratios of organ-to-total viscera weight at weaning.

<p>Mean values (±SEM) of the relative weight (W) of organs to total viscerae-weight (TV-W) for treatment (Hydroxytyrosol, HT vs. Control group, C) and litter size (2–6 vs. 7–10 piglets/ litter).</p