title: Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation.
abstract: Dexamethasone treatment of F0 pregnant rodents alters F1 placental function and adult cardiometabolic phenotype. The adult phenotype is transmitted to the F2 generation without further intervention, but whether F2 placental function is altered by F0 dexamethasone treatment remains unknown. In the present study, F0 mice were untreated or received dexamethasone (0.2µgg(-1)day(-1), s.c.) over Days 11-15 or 14-18 of pregnancy (term Day 21). Depending on the period of F0 dexamethasone treatment, F1 offspring were lighter at birth or grew more slowly until weaning (P<0.05). Glucose tolerance (1gkg(-1), i.p.) of adult F1 males was abnormal. Mating F1 males exposed prenatally to dexamethasone with untreated females had no effect on F2 placental function on Day 19 of pregnancy. In contrast, when F1 females were mated with untreated males, F2 placental clearance of the amino acid analogue (14)C-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 F2 placental Slc38a4 expression was decreased in these dams (P<0.05). F0 dexamethasone treatment had no effect on F2 fetal or placental weights, regardless of lineage. Therefore, the effects of F0 dexamethasone exposure are transmitted intergenerationally to the F2 placenta via the maternal, but not paternal, line.
authors: Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.
authors: O R
authors: OR
authors: Vaughan
authors: Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.
authors: H M
authors: HM
authors: Phillips
authors: Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.
authors: A J
authors: AJ
authors: Everden
authors: Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.
authors: A N
authors: AN
authors: Sferruzzi-Perri
authors: Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.
authors: A L
authors: AL
authors: Fowden
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D012098:Reproduction / Q000187:drug effects*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone