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. 1. 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]. Glucocorticoids have been implicated as playing a fundamental role in the fetal programming process. Although required for the normal development and maturation of a number of organ systems, glucocorticoid overexposure is known to have a negative impact on normal growth and development and is associated with low birth weight, hypertension, and altered reactivity of the hypothalamic-pituitary-adrenal axis [3, 4]. The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the fetus primarily through the action of the microsomal enzyme, 11- hydroxysteroid dehydrogenase type 2 (HSD2). The HSD2 enzyme catalyzes the
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