Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice

Mark R Garbrecht,Fred S Lamb

doi:10.1155/2013/867938

Abstract

The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-β hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation.

Highlights

A wealth of evidence demonstrates that an individual’s risk of developing adult onset cardiovascular disease and the metabolic syndrome can be “programmed” by events occurring in utero
The role of placental glucocorticoid metabolism in the pathogenesis of fetal programming of adult onset disease continues to be an area of active research
We observed that placental hydroxysteroid dehydrogenase type 2 (HSD2) gene expression and enzyme activity was unaffected by maternal protein restriction (18% protein versus 9% protein) in C57BL/6 mice

Summary

Introduction

A wealth of evidence demonstrates that an individual’s risk of developing adult onset cardiovascular disease and the metabolic syndrome can be “programmed” by events occurring in utero. Studies aimed at gaining a better understanding of the fetal origins of adult-onset diseases have provided evidence that maternal diet during gestation can have a profound impact on the incidence of these conditions. Maternal dietary protein restriction during pregnancy has been linked to decreased birth weight and subsequent hypertension, coronary artery disease, obesity, and diabetes in adulthood [1, 2]. The role of placental HSD2 enzyme activity in protecting the fetus from maternal glucocorticoid overexposure has been highlighted in both human and animal studies. Decreased birth weight and a variety of programmed phenotypes have been linked to mutation or genetic knockout of the HSD2 gene, the pharmacological inhibition of ISRN Endocrinology

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