Placental and fetal membrane nephrin and neph1 gene expression: Response to inflammation

OBJECTIVE: Fetal and amniotic fluid (AF) proteins (eg, alpha fetoprotein [AFP]) are measurable ill the maternal circulation. Elevated maternal serum AFP levels indicate a risk for fetal anomalies or for obstetrical complications that are often associated with inflammation (eg, preterm labor). However, little is known of the mechanism of protein exchange between the fetus, AF, and maternal circulation. Nephrin and Neph 1 are cell membrane proteins that restrict glomerular protein filtration and which are differentially expressed with renal inflammation. We sought to investigate whether nephrin and Neph 1 were expressed in placenta and fetal membranes, and whether inflammation modified the expression. METHODS: Pregnant rats at 18 days' gestation were injected with lipopolysacchride (LPS) or control saline intraperitoneally (IP) and killed at 1, 6, and 12 hours after injection. Placenta and fetal membranes were obtained and real-time polymerase chain reaction (PCR) performed for determination of nephrin and Neph 1 levels. RESULTS: Nephrin and Neph 1 were expressed in both placenta and fetal membranes. Following maternal LPS administration, nephrin mRNA significantly increased in the membranes (0.22 +/- 0.02 to 0.51 +/- 0.050, P <.05), while Neph 1 expression significantly declined in the placenta (0.19 +/- 0.05 to 0.10 +/- 0.01, P <.05). CONCLUSION: Fetal membranes and placenta of the rat express mRNA for the protein barriers nephrin and Neph 1, suggesting a role in the regulation of protein transfer from the fetus to mother. Under basal conditions, AF AFP transfer acrossfetal ineinbranes rnay accountfir niaternal sernin AFP levels, whereas gestational inflammatory conditions (eg, preterm labor, threatened abortion) may augment AFP transfer across the placenta. Copyright (c) 2005 by the Society for Gynecologic Investigation.