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

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.

Epigenetic regulation of the placental HSD11B2 barrier and its role as a critical regulator of fetal development

“…33,67 Furthermore, specific reduction in protein content of the maternal diet during early and mid, but not late, gestation in Wistar rats caused a reduction of placental HSD11B2 expression. 68 These findings have been supported by some, [69][70][71] though not all, 72 studies and collectively suggest that adequate protein intake is required to maintain optimal expression of placental HSD11B2. However, an excess of calories, predominantly derived from high fat and high sugar foods largely define Western dietary habits.…”

A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice

“…Other studies of the same strain of mice have found that a higher fat diet either reduces 11β-HSD2 mRNA expression [ 22 ] or has no effect [ 26 ]. A maternal low-protein diet did not affect placental 11β-HSD2 expression or activity in mice [ 41 ], in contrast to other species.…”