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 in 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 Neph1 are cell membrane proteins that restrict glomerular protein filtration and which are differentially expressed with renal inflammation. We sought to investigate whether nephrin and Neph1 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 Neph1 levels.

RESULTS

Nephrin and Neph1 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 Neph1 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 across fetal membranes may account for maternal serum AFP levels, whereas gestational inflammatory conditions (eg, preterm labor, threatened abortion) may augment AFP transfer across the placenta.