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28 August 2013 Adaptations in Placental Phenotype Depend on Route and Timing of Maternal Dexamethasone Administration in Mice
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Abstract

Synthetic glucocorticoids, like dexamethasone (dex), restrict growth of the fetus and program its adult physiology, in part by altering placental phenotype. The route and timing of dex administration determine the fetal and adult outcomes, but whether these factors affect placental phenotype remains unknown. This study compared placental morphology, amino acid transport, and gene expression in mice given dex orally or by subcutaneous injection over the periods of most rapid placental (Days [D] 11–16) or fetal (D14–19) growth (term is D21). Compared with untreated and saline-injected controls, both dex treatments reduced placental weight at D16 and 19 and fetal weight and total labyrinthine volume at D19 to a similar extent. Only oral dex treatment from D11 to D16 reduced labyrinthine fetal capillary volume on D16 and increased placental 14C-methylaminoisobutyric acid (MeAIB) clearance at D19, 3 days after treatment ended. Neither route of dex treatment altered placental expression of Slc38a, Hsd11b, or the glucocorticoid receptor, Nr3c1, at D16. In contrast, both routes of dex treatment from D14 to D19 increased placental Hsd11b2 expression and labyrinthine maternal vessel volume. Furthermore, injection per se altered placental expression of Nr3c1, Hsd11b1, and specific Slc38a isoforms in an age-related manner. Overall, MeAIB clearance was not related to Slc38a transporter expression but was correlated inversely with maternal corticosterone concentrations when dex was undetectable in maternal plasma at D19. The effects of dex on placental phenotype, therefore, depend on both the route and timing of administration and may relate to local glucocorticoid availability during and after the treatment period.

Owen R. Vaughan, Amanda N. Sferruzzi-Perri, Philip M. Coan, and Abigail L. Fowden "Adaptations in Placental Phenotype Depend on Route and Timing of Maternal Dexamethasone Administration in Mice," Biology of Reproduction 89(4), (28 August 2013). https://doi.org/10.1095/biolreprod.113.109678
Received: 28 March 2013; Accepted: 1 August 2013; Published: 28 August 2013
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