EXPRESSION OF ERYTHROPOIETIN BY THE HUMAN PLACENTA

Circulating levels of maternal erythropoietin (EPO) rise during gestat ion due to increased biosynthesis of the hormone, Our objective was to investigate the human placenta as a potential extrarenal site of EPO production, Using two monoclonal antibodies recognizing different anti genic determinants, we identified immunoreactive EPO associated with v illous cytotrophoblast, endovascular and intravascular cytotrophoblast , cytotrophoblast cell colunms, and syncytiotrophoblast of first and s econd-trimester placenta as well as syncytiotrophoblast and extravillo us cytotrophoblast of normal third-trimester and preeclamptic placenta , In addition, cultured JAR (trophoblast-derived) choriocarcinoma cell s, cytotrophoblasts isolated from term placenta, villous core cells, a nd possibly other nontrophoblast cells within the decidual basal plate expressed immunoreactive EPO, Using reverse transcription-polymerase chain reaction and EPO-specific primers, a 378 bp DNA product was ampl ified from placental tissues of various gestational ages, cytotrophobl asts isolated from term placenta, and JAR choriocarcinoma cells, The a mplified product yielded restriction enzyme fragments of predicted siz es, On Southern analysis, hybridization was observed for two of these fragments in which the radiolabeled EPO cDNA probe did not overlap wit h the primer sequences, Finally, the JAR choriocarcinoma cells elabora ted EPO into the culture medium as determined by enzyme-linked immunos orbant assay and expressed EPO mRNA as determined by Northern analysis , both of which were stimulated by hypoxia (15-20 torr), Taken togethe r, these results suggest a new site of EPO expression: the trophoblast cell of the human placenta.