title: Placental folate transport during pregnancy.
abstract: The aim of this study was to elucidate the mechanism of folate transport in the placenta over the course of pregnancy. We found that folate receptor alpha (FRalpha) and reduced folate carrier (RFC) localized on the apical side of human placental villi. Since folate binding to placental brush-border membrane vesicles (BBMVs) was strongly inhibited by phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, it is possible that FRalpha, a glycosyl phosphatidylinositol linked glycoprotein, is a candidate for folate uptake from maternal blood to the placenta. Moreover, additional inhibitory effects of thiamine pyrophosphate (TPP) and hemin on folate uptake after PI-PLC treatment suggested that not only FRalpha but also RFC and heme carrier protein 1 (HCP1) are involved in the folate transport mechanism in the human placenta. It was also found that accumulation of folate after intravenous injection increased with the progress of gestation in the rat placenta and the fetus. Furthermore, increases in the expression levels of mRNA of rFRalpha, rRFC, and rHCP1 in the rat placenta during pregnancy were observed. These findings suggest that FRalpha, RFC, and HCP1 are important carriers of folate in the placenta during pregnancy. The results of this study suggest that increases in the expression levels of FRalpha, RFC, and HCP1 in the placenta play an important role in the response to increased need for folate for the placenta and fetus during development with the progress of gestation.
authors.affiliation: Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmascience, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yasuda
authors.forename: Satoko
authors.initials: S
authors.lastname: Hasui
authors.forename: Chiaki
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yoshioka
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000818:Animals; D001692:Biological Transport; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058978:Reduced Folate Carrier Protein
chemical_list: D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid