Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2011) 25 OC5.2

SFEBES2011 Oral Communications Reproduction and fetal programming (8 abstracts)

Maternal low protein diet and fetal growth restriction: new insights into the role of placental 11β-hydroxysteroid dehydrogenase-2

Elizabeth Cottrell , Megan Holmes & Jonathan Seckl


University of Edinburgh, Edinburgh, UK.


Placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) rapidly converts glucocorticoids to inactive metabolites, thus protecting the developing fetus from high maternal glucocorticoids. Genetic deficiency or inhibition of 11β-HSD2 associates with fetal growth restriction, low birth weight, and cardiometabolic disease in adulthood. Similar ‘programming’ effects are seen with maternal malnutrition or stress; these challenges associate with reduced placental 11β-HSD2 at term. We therefore explored the importance of 11β-HSD2 in dietary programming.

Feeding C57Bl/6J mice an isocaloric low protein (LP) diet throughout gestation (8% protein versus 18% control diet) significantly decreased placental weight (P<0.001) and fetal weight at embryonic day (E) 17.5 (0.89±0.05 g in control versus 0.74±0.03 g in low protein; P<0.001). This reduction in fetal weight was preceded by a downregulation of 11β-HSD2 enzyme activity from E16.5 (decreased in LP by 28 and 20% at E16.5 and 17.5, respectively; P<0.05). However, at earlier gestational ages (E13.5–15.5), LP diet increased placental 11β-HSD2 activity (increased in LP by 21, 23 and 41% at E13.5, 14.5 and 15.5, respectively; P<0.05), perhaps to maximise midgestation fetal growth. Using a heterozygous 11β-HSD2+/− mating strategy to generate 11β-HSD2+/+, +/− and −/− offspring within the same litters, maternal LP diet reduced fetal body weight to a similar extent in all genotypes compared with control offspring, although the magnitude was blunted in 11β-HSD2−/− offspring. Thus, LP diet has effects over-and-above 11β-HSD2 inhibition to reduce fetal weight gain.

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