title: Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition.
abstract: 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.
authors.affiliation: Clinic of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria. christian.wadsack@meduni-graz.at
authors.forename: Christian
authors.initials: C
authors.lastname: Wadsack
authors.forename: Silvia
authors.initials: S
authors.lastname: Tabano
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maier
authors.forename: Ursula
authors.initials: U
authors.lastname: Hiden
authors.forename: Gioia
authors.initials: G
authors.lastname: Alvino
authors.forename: Veronica
authors.initials: V
authors.lastname: Cozzi
authors.forename: Manfred
authors.initials: M
authors.lastname: Hüttinger
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Schneider
authors.forename: Uwe
authors.initials: U
authors.lastname: Lang
authors.forename: Irene
authors.initials: I
authors.lastname: Cetin
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
mesh_terms: D000328:Adult; D002784:Cholesterol / Q000032:analysis; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn; D008074:Lipoproteins / Q000032:analysis*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000032:analysis; D008431:Maternal-Fetal Exchange; D008875:Middle Aged; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D011973:Receptors, LDL / Q000032:analysis; D018110:Receptors, Lipoprotein / Q000032:analysis*
chemical_list: D008074:Lipoproteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C030104:lipoprotein cholesterol; D002784:Cholesterol