Melanie C Audette1, John R G Challis, Rebecca L Jones, Colin P Sibley, Stephen G Matthews. 1. Departments of Physiology (M.C.A., J.R.G.C., S.G.M.), Obstetrics and Gynecology (J.R.G.C., S.G.M.), and Medicine (M.C.A., J.R.G.C., S.G.M.) University of Toronto, Toronto, Ontario Canada M5A 1A8; and Maternal and Fetal Heath Research Centre (J.R.G.C., R.L.J., C.P.S.), School Institute of Human Development, Manchester Academic Health Sciences Centre, University of Manchester, St. Mary's Hospital, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester M13 9WL, United Kingdom.
Abstract
CONTEXT: Synthetic glucocorticoids (sGCs) are routinely given to women with threatened preterm labor and have been linked to fetal growth restriction and developmental programming. Reductions in fetal growth are likely to be mediated by placental dysfunction, including altered nutrient transport. sGCs modify the system A neutral amino acid transporter in vitro, but there are no in vivo comparable data in human placenta. OBJECTIVE: Because ∼ 30% of women who receive sGCs carry to term, our objective was to examine the short- and longer-term consequences of antenatal sGCs on placental system A transport. METHODS AND PATIENTS: Placental tissue was collected from women treated with sGCs between 24 hours and 14 days before delivery (24h-14d), 14 days after treatment but before term (14d-term), or at term, compared with healthy term (control) deliveries to measure system A-mediated activity (Na(+)-dependent [(14)C]methylaminoisobutyric acid uptake per gram placenta) and mRNA expression. RESULTS: After sGC treatment, system A activity was significantly reduced at term compared with both sGC placentas delivered 24h-14d and compared with controls. Placentae from women treated with sGCs who delivered between 14d-term also had significantly reduced system A activity compared with 24h-14d placentas. SLC38A1 and SLC38A2 mRNA expression was unaffected. However, SLC38A4 was significantly reduced by sGCs at term compared with placentas delivered between 14d-term. CONCLUSION: We conclude that women who are at risk of preterm labor and receive sGCs but deliver at term have significantly reduced placental system A amino acid transporter activity. Altered placental transporter function could affect fetal growth and may contribute to developmental programming reported in both animal and clinical studies.
CONTEXT: Synthetic glucocorticoids (sGCs) are routinely given to women with threatened preterm labor and have been linked to fetal growth restriction and developmental programming. Reductions in fetal growth are likely to be mediated by placental dysfunction, including altered nutrient transport. sGCs modify the system A neutral amino acid transporter in vitro, but there are no in vivo comparable data in human placenta. OBJECTIVE: Because ∼ 30% of women who receive sGCs carry to term, our objective was to examine the short- and longer-term consequences of antenatal sGCs on placental system A transport. METHODS AND PATIENTS: Placental tissue was collected from women treated with sGCs between 24 hours and 14 days before delivery (24h-14d), 14 days after treatment but before term (14d-term), or at term, compared with healthy term (control) deliveries to measure system A-mediated activity (Na(+)-dependent [(14)C]methylaminoisobutyric acid uptake per gram placenta) and mRNA expression. RESULTS: After sGC treatment, system A activity was significantly reduced at term compared with both sGC placentas delivered 24h-14d and compared with controls. Placentae from women treated with sGCs who delivered between 14d-term also had significantly reduced system A activity compared with 24h-14d placentas. SLC38A1 and SLC38A2 mRNA expression was unaffected. However, SLC38A4 was significantly reduced by sGCs at term compared with placentas delivered between 14d-term. CONCLUSION: We conclude that women who are at risk of preterm labor and receive sGCs but deliver at term have significantly reduced placental system A amino acid transporter activity. Altered placental transporter function could affect fetal growth and may contribute to developmental programming reported in both animal and clinical studies.
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