The transport of
folate across the placenta involves a number of different receptors including
folate receptor-alpha (FR-α),
reduced folate carrier (RFC) and
proton coupled folate transporter (PCFT). In addition there are a number of
ATP-dependent transporters which have also recently been shown to be involved in
folate transport; these include ABCB1, ABCC2 and BCRP (ABCG2). The aim of the current study was to characterise the placental
mRNA and
protein expression of these
folate transporters throughout gestation and also to see if expression is altered in
pre-eclampsia. Placental tissue was collected from women undergoing termination of pregnancy (TOP) and from women undergoing elective
Caesarean section. To investigate
mRNA expression quantitative real time PCR was used with gene specific
oligonucleotide primers to FR-α, RFC, PCFT, ABCB1, ABCC2, BCRP and the reference gene YWHAZ.
Protein expression was also characterised using immunohistochemistry of
paraffin embedded placental tissue. Both
protein and
mRNA expression of all transporters examined decreased as the gestation progressed. Expression of FR-α and PCFT
mRNA and
protein were decreased in
pre-eclampsia compared with normal term pregnancy. The higher levels of expression of FR-α, RFC, PCFT, ABCB1, ABCC2 and BCRP in early pregnancy indicate that these transporters may have an important role in the establishment and development of the placenta, with expression reducing in preparation for parturition. Reductions in FR-α and PCFT in
pre-eclampsia may be a mechanism involved in the pathogenesis of
pre-eclampsia by limiting placental
folate uptake resulting in reduced levels of angiogenesis, cell proliferation and
antioxidant protection.