Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytiotrophoblast and choriocarcinoma cells.

The folate receptor (FR), an essential component in the process of folate uptake in various cells, is known to exist in three isoforms, FR-alpha, FR-beta and FR-gamma, with differential tissue expression. Transfer of folate across the human placenta from mother to fetus involves participation of a folate receptor expressed in the syncytiotrophoblast, but the isoform identity of this receptor has not been established. Based on the tissue/cell type from which these isoforms have been cloned, it is currently believed that FR-alpha is the isoform expressed in adult tissues whereas FR-beta is the isoform expressed in fetal tissues including placenta. The present study, undertaken primarily to establish the isoform identity of the FR expressed in the placental syncytiotrophoblast, does not support this currently prevailing nomenclature. Reverse transcription coupled with polymerase chain reaction (RT-PCR) of total/poly(A)+ RNA from placenta, cultured trophoblast cells and JAR choriocarcinoma cells with primer pairs specific for either FR-alpha or FR-beta reveals that while both isoforms are detectable in the whole placental tissue, only FR-alpha is present in the normal trophoblast cells and in the choriocarcinoma cells. Northern analysis with probes designed to distinguish between the mRNA transcripts coding for these two isoforms corroborate the RT-PCR findings. Furthermore, the nucleotide sequences of the PCR products obtained from the trophoblast cells and JAR cells are identical to the nucleotide sequence of the FR-alpha cDNA. These studies establish that it is the FR-alpha isoform, and not the FR-beta isoform, which is selectively expressed in the placental trophoblast cells. FR-beta, which is known to be present in the placenta, most likely arises from the maternal decidua normally associated with this tissue.