Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition

1 Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria; 2 Clinic of Obstetrics and Gynecology, University of Milano, Milan, Italy; 3 Center of Physiology and Pathophysiology; and 4 Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Vienna, Austria Submitted 9 November 2005 ; accepted in final form 5 September 2006 Among other factors, fetal growth requires maternal supply of cholesterol. Cellular cholesterol uptake is mainly mediated by the LDL receptor (LDL-R) and the scavenger receptor family. We hypothesized that expression levels of key receptors of these families were regulated differently in placentas from IUGR pregnancies with varying degrees of severity. Third-trimester placentas from IUGR pregnancies with (IUGR-S) and without (IUGR-M) fetal hemodynamic changes and from control (AGA) pregnancies were studied. LDL-R, LDL-R-related protein (LRP-1), and scavenger receptor class B type I (SR-BI) mRNA and protein levels were measured. Cholesterol concentration and composition of lipoproteins were analyzed enzymatically and by lipid electrophoresis, respectively, in maternal and umbilical cord blood. LDL-R mRNA levels in IUGR-M were similar to AGA but lower ( P < 0.05) in IUGR-S. In contrast, LDL-R protein was twofold (IUGR-M) and 1.8-fold (IUGR-S) higher ( P < 0.05) than in the AGA group. LRP-1 mRNA and protein levels were not altered in the IUGR cases. SR-BI mRNA was unchanged in IUGR, but protein levels were lower ( P < 0.05) in IUGR-S than in the other groups. Maternal plasma concentrations of LDL cholesterol were higher ( P < 0.05) in the AGA group (188.5 ± 23.6 mg/dl) than in the IUGR-S group (154.2 ± 26.1). Electrophoretic mobility of the LDL fraction in maternal plasma demonstrated significant changes in migration toward higher values (AGA 0.95 ± 0.06, IUGR-M 1.12 ± 0.11, P < 0.001; IUGR-S 1.28 ± 0.20, P = 0.002). We conclude that LDL-R and SR-BI levels are altered in IUGR pregnancies. These differences were associated with changes in LDL, but not HDL, mobility and cholesterol concentration in maternal circulation. pregnancy; placenta; lipids; fetal growth Address for reprint requests and other correspondence: C. Wadsack, Clinic of Obstetrics and Gynecology Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria (e-mail: christian.wadsack{at}meduni-graz.at )