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

Consolación Garcia-Contreras,Cristina Ovilo,Marta Vazquez-Gomez,Beatriz Isabel,Jaime Ballesteros,Angelo Zinellu,José Pesantez,Alicia Barbero,Fiammetta Berlinguer,Pedro Gonzalez-Añover,Antonio Gonzalez-Bulnes,Teresa Encinas,Yolanda Nuñez,Jorge Gonzalez,Miriam Ayuso,Susana Astiz,Laura Torres-Rovira

doi:10.3390/ijms20051187

Abstract

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.

Highlights

Hydroxytyrosol is a polyphenol present in olive leaves and fruits with prominent antioxidant, metabolism-regulatory, anti-inflammatory and immuno-modulatory properties [1]
A second concerning issue for the use of polyphenols during pregnancy is the existence of evidence pointing to the induction of epigenetic changes by DNA-methylation [2]; most of them are adaptive and beneficial, but deleterious effects cannot be discarded. Clarification of these points is essential for issuing dietary guidelines during pregnancy and, we aimed to use our swine model to determine possible effects of maternal hydroxytyrosol supplementation on placental expression of genes involved in antioxidant homeostasis, vascularization and fetal growth and on antioxidant status, DNA-methylation and phenotypic traits of the fetus
The assessment of maternal features in the groups C and HTX at sampling (Table 1) showed no significant differences in body weight, back-fat depth, plasma antioxidant status, plasma parameters of metabolism of glucose, and lipids

Summary

Introduction

Hydroxytyrosol is a polyphenol present in olive leaves and fruits (and, in virgin olive oil) with prominent antioxidant, metabolism-regulatory, anti-inflammatory and immuno-modulatory properties [1]. The reason for using hydroxytyrosol, or other polyphenols, in pregnancies at risk of IUGR is due to the fact that the disease is primarily related to an impaired supply of nutrients and oxygen and, a weakened antioxidant defense system [4,5,6,7]. Polyphenol supplementation increases plasma antioxidant capacity [8,9] and improves placental oxidative stress [10]. In this regard, it is well established that improving the oxidative stress status during pregnancy is related to alleviation of the IUGR process [11,12,13]. In a similar way to other polyphenol compounds, there is a scarcity of experimental data on both the realistic benefits and potential hazards of hydroxytyrosol supplementation during gestation [9,14,15] despite the promising results obtained in our model [3]

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Discussion

Conclusion