Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation

Dexamethasone treatment of F-0 pregnant rodents alters F-1 placental function and adult cardiometabolic phenotype. The adult phenotype is transmitted to the F-2 generation without further intervention, but whether F-2 placental function is altered by F-0 dexamethasone treatment remains unknown. In the present study, F-0 mice were untreated or received dexamethasone (0.2 mu gg(-1) day(-1), s.c.) over Days 11-15 or 14-18 of pregnancy (term Day 21). Depending on the period of F-0 dexamethasone treatment, F-1 offspring were lighter at birth or grew more slowly until weaning (P < 0.05). Glucose tolerance (1 g kg(-1), i.p.) of adult F-1 males was abnormal. Mating F-1 males exposed prenatally to dexamethasone with untreated females had no effect on F-2 placental function on Day 19 of pregnancy. In contrast, when F-1 females were mated with untreated males, F-2 placental clearance of the amino acid analogue C-14-methylaminoisobutyric acid was increased by 75% on Day 19 specifically in dams prenatally exposed to dexamethasone on Days 14-18 (P < 0.05). Maternal plasma corticosterone was also increased, but F-2 placental Slc38a4 expression was decreased in these dams (P, 0.05). F-0 dexamethasone treatment had no effect on F-2 fetal or placental weights, regardless of lineage. Therefore, the effects of F-0 dexamethasone exposure are transmitted intergenerationally to the F-2 placenta via the maternal, but not paternal, line.