title: Placental folate transport and binding are not impaired in pregnancies complicated by fetal growth restriction.
abstract: Maternal folate deficiency is associated with fetal growth restriction, however, transfer of folate across placentae of pregnancies complicated by fetal growth restriction has never been investigated. We studied whether maternal to fetal 5-methyltetrahydrofolate (5MTF) transport in the ex vivo dually perfused isolated cotyledon, binding of [(3)H] folate (PteGlu) to the syncytial microvillous membrane, and protein expression of folate receptor alpha (FR-alpha) and reduced folate carrier (RFC) in these placentae are disturbed. Placental clearance of 5MTF from the maternal perfusate appeared to be non-saturable over a range of 50 to 500 nm, independent of albumin and flow-independent. No statistically significant differences between placentae complicated with fetal growth restriction and uncomplicated pregnancies were observed. Binding characteristics of [(3)H-]PteGlu to microvillous membranes of fetal growth restriction versus control placentae were similar: B(max)of 3.9+/-2.0 (mean+/-s.d.) versus 4.0+/-1.6 pmol/mg protein and a K(d)of 0.037+/-0.010 versus 0.040+/-0.018 nm. Expression of FR-alpha and RFC were not different in placentae of both groups studied. In conclusion, fetal growth restriction appears not to be associated with impaired maternal to fetal placental folate transport, placental receptor binding, or expression of FR-alpha and RFC.
authors.affiliation: Department of Pharmacology and Toxicology, University Medical Centre Nijmegen, 233, University Medical Centre Nijmegen/NCMLS, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: Bisseling
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: J J M
authors.initials: JJ
authors.lastname: van den Heuvel
authors.forename: H L M
authors.initials: HL
authors.lastname: Siero
authors.forename: F M
authors.initials: FM
authors.lastname: van de Water
authors.forename: A J
authors.initials: AJ
authors.lastname: Walker
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
authors.forename: P
authors.initials: P
authors.lastname: Smits
authors.forename: F G M
authors.initials: FG
authors.lastname: Russel
mesh_terms: D000328:Adult; D001692:Biological Transport; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism; D058978:Reduced Folate Carrier Protein; D013763:Tetrahydrofolates / Q000378:metabolism; D014316:Tritium; D014327:Trophoblasts / Q000648:ultrastructure
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D013763:Tetrahydrofolates; D014316:Tritium; D005492:Folic Acid; C005984:5-methyltetrahydrofolate