Placental P-glycoprotein is unaffected by timing of antenatal glucocorticoid therapy but reduced in SGA preterm infants

• Published in: Placenta (Eastbourne) 2013-04, Vol.34 (4), p.325-330
• Main Authors: Hodyl, N.A, Stark, M.J, Butler, M, Clifton, V.L
• Format: Article
• Language: English
• Subjects: Antenatal steroids; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Betamethasone - administration & dosage; Biological and medical sciences; Embryology: invertebrates and vertebrates. Teratology; Female; Fetal Blood - chemistry; Fetal Organ Maturity - drug effects; Fundamental and applied biological sciences. Psychology; Glucocorticoids - administration & dosage; Humans; Hydrocortisone - blood; Infant, Newborn; Infant, Premature - metabolism; Infant, Small for Gestational Age - metabolism; Internal Medicine; Male; Obstetric Labor, Premature - drug therapy; Obstetrics and Gynecology; P glycoprotein; Placenta; Placental glucocorticoid barrier; Pregnancy; Preterm neonate; Prospective Studies; RNA, Messenger - metabolism; Sex Factors; SGA
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2013.01.013

Abstract Introduction The beneficial effects of antenatal glucocorticoid therapy on fetal lung maturation require their passage across the placental glucocorticoid barrier, composed of glucocorticoid metabolising enzymes, such as 11 beta hydroxysteroid dehydrogenase (11βHSD), and proteins that efflux glucocorticoids, such as P-glycoprotein (P-gp). We have shown that 11βHSD2 activity is responsive to antenatal glucocorticoids, however the effect on placental P-gp remains unknown. Since antenatal glucocorticoids have a greater prophylactic effect in females compared to males, we also assessed whether this therapy induced sexually dimorphic effects on P-gp expression, as well as on placental inflammatory processes mediated by corticosteroids. Methods Placentas were collected from 53 women presenting in threatened preterm labour, and processed to assess cytokine and P-gp mRNA expression, as well as P-gp localisation using immunohistochemistry. Results Placental cytokine, P-gp mRNA and protein expression were not altered by timing of antenatal glucocorticoids or fetal sex. However, both P-gp mRNA and protein expression were significantly reduced in placentas from infants born small for gestational age (SGA) compared to appropriately grown infants ( p