Endocrine Abstracts

Synthetic glucocorticoid administration during pregnancy reduces birth weight and increases disease risk in the offspring. This study investigated whether increasing maternal natural corticosterone levels, by endogenous stress or exogenous administration, alters fetal amino acid supply in the mouse.

C57BL6/J dams (n=82) were exposed to daily restraint and subcutaneous saline injection (stress) or given corticosterone (cort, 82±11 μg/g per day in drinking water) for 5 days in mid/late pregnancy (either D11–16 or D14–19, term is D21). Plasma corticosterone was measured by RIA. On D19, placental amino acid transport was determined as the materno-fetal clearance of non-metabolisable ¹⁴C-methylaminoisobutyric acid (MeAIB). Gene expression was determined in snap-frozen placentae using qPCR. Significant effect (P<0.05) of treatment was determined by one way ANOVA with Bonferroni’s post-hoc test.

Compared with untreated controls (ut), stress or cort from D11–16 increased plasma corticosterone on D16 (ut, 571±58 ng/ml; stress, 1018±109 ng/ml; cort, 1142±134 ng/ml; P<0.05) but not on D19 (ut, 714±41 ng/ml; stress, 739±53 ng ml; cort, 524±53 ng/ml; P>0.05). Corticosterone remained was high on D19 in both groups of dams treated from D14–19 (stress, 949±134 ng/ml; cort, 1143±176 ng/ml. P=0.003). On D19, MeAIB clearance was affected by treatment (P=0.007), and was highest in D11–14 cort dams and lowest in D14–19 cort dams. When all groups were combined, MeAIB clearance inversely correlated with maternal corticosterone (Pearson’s r=−0.50, P<0.001). On D19, placental Redd1/Ddit4, an inhibitor of mammalian target of rapamycin (mTOR) signalling, was upregulated when maternal corticosterone was high in D14–19 cort treated dams (142% vs ut, P<0.05) but did not differ from control values in D11–16 cort dams.

The results show that physiological increases in corticosterone during mouse pregnancy regulate fetal amino acid supply, in part, through inhibition of placental mTOR signalling. This effect may defend amino acids for maternal metabolism, at the expense of fetal growth.

Declaration of funding: This work was supported by a graduate studentship from the Centre for Trophoblast Research.