Background and aim: Ursodeoxycholic acid (UDCA) promotes bile acids (BA) efflux from the fetal compartment during Intrahepatic Cholestasis of Pregnancy (ICP). Cholestasis of pregnancyThe modification of the basolateral BA transporters of the human placental syncytiotrophoblast in treated and untreated ICP is still uninvestigated. Aim of the present study was to determine if placental organic anion transporter A (OATP-A), able to transport BA, is regulated by UDCA in ICP. Material and methods: 29 pregnant women with ICP (16 untreated, 33.5±1.3 years; 13 treated with UDCA – 20 mg/kg/day, 35.6±1.3 years) and 14 agematched healthy controls (31.7±2.1 years) have agreed to participate to the study (none had gallstone disease, abnormal liver tests, liver steatosis on ultrasonography). Placentas were obtained at delivery and processed for mRNA and protein extraction. Real Time-PCR and immunoblotting were performed. Statistical differences between groups were evaluated by one way ANOVA with Dunn’s Multiple Comparison test. Results: OATP-AmRNA and protein expression were similar in untreated ICP and controls. UDCA administration induced a significant increase in human placental OATP-A mRNA (ANOVA=0.016, 436.1±181.3 vs 100.1±22.8%) and protein (ANOVA=0.0008, 128.2±6.03 vs 99.85±4.53%) expression compared to controls. With regard to protein expression, the difference was statistically significant also compared to untreated ICP (ANOVA=0.0008, 128.2±6.03 vs 97.75±8.84%). Conclusions: UDCA administration significantly increase OATP-A mRNA and protein expression in human placenta favouring transplacental BA transport.

UDCA UP-REGULATES HUMAN PLACENTAL OATP-A EXPRESSION IN INTRAHEPATIC CHOLESTASIS OF PREGNANCY

AZZAROLI, FRANCESCO;RASPANTI, MARIA ELENA;LONGO, MARIA LUISA;MONTAGNANI, MARCO;TURCO, LAURA;BUONFIGLIOLI, FEDERICA;LODATO, FRANCESCA;RODA, ENRICO;LISOTTI, ANDREA;CECINATO, PAOLO;MAZZELLA, GIUSEPPE
2010

Abstract

Background and aim: Ursodeoxycholic acid (UDCA) promotes bile acids (BA) efflux from the fetal compartment during Intrahepatic Cholestasis of Pregnancy (ICP). Cholestasis of pregnancyThe modification of the basolateral BA transporters of the human placental syncytiotrophoblast in treated and untreated ICP is still uninvestigated. Aim of the present study was to determine if placental organic anion transporter A (OATP-A), able to transport BA, is regulated by UDCA in ICP. Material and methods: 29 pregnant women with ICP (16 untreated, 33.5±1.3 years; 13 treated with UDCA – 20 mg/kg/day, 35.6±1.3 years) and 14 agematched healthy controls (31.7±2.1 years) have agreed to participate to the study (none had gallstone disease, abnormal liver tests, liver steatosis on ultrasonography). Placentas were obtained at delivery and processed for mRNA and protein extraction. Real Time-PCR and immunoblotting were performed. Statistical differences between groups were evaluated by one way ANOVA with Dunn’s Multiple Comparison test. Results: OATP-AmRNA and protein expression were similar in untreated ICP and controls. UDCA administration induced a significant increase in human placental OATP-A mRNA (ANOVA=0.016, 436.1±181.3 vs 100.1±22.8%) and protein (ANOVA=0.0008, 128.2±6.03 vs 99.85±4.53%) expression compared to controls. With regard to protein expression, the difference was statistically significant also compared to untreated ICP (ANOVA=0.0008, 128.2±6.03 vs 97.75±8.84%). Conclusions: UDCA administration significantly increase OATP-A mRNA and protein expression in human placenta favouring transplacental BA transport.
2010
F. Azzaroli; A. Mennone; M.E. Raspanti; M.L. Longo; M. Montagnani; L. Turco; F. Buonfiglioli; M. Giandinoto; F. Lodato; E. Roda; A. Lisotti; P. Cecinato; J.L.Boyer; G. Mazzella
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/88691
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