Metabolism of vitamin D3 in the placental tissue of normal and preeclampsia complicated pregnancies and premature births.

The aim of this study was to analyze the hormonal basis for low 1,25(OH)2D3 circulating levels in patients with preeclampsia and/or preterm deliveries. The activity and expression of the 1 alphaOHase, 25-OHase, 24-OHase and VDR in the placental tissue of normal pregnancies, preeclampsia-complicated pregnancies and premature births were investigated. The mRNA of the enzymes was detected in the placental tissue from preeclamptic pregnancies and compared to those of normal placental tissue. Real time PCR analysis showed a significant increased 1 alpha-OHase gene expression in preeclamptic patients, and the gene expression of 24-OHase was significantly decreased. With regard to the 25-OHase the median value of the normal placental tissue was significantly higher than in the placental tissue of preeclamptic patients. The real time analysis of all target genes also showed significant differences in normal placental tissue compared to placental tissue from premature births (VDR: p = 0.041; 1 alpha-OHase: p = 0.013; 24-OHase: p = 0.007; 25-OHase p = 0.027). Our observation of reduced VDR expression on mRNA level in placental tissue indicates a possible dependence of the modulation of VDR expression from proliferation and differentiation processes. It can be speculated whether the down-regulation of VDR in the examined placenta cells was the result of an altered production of calcitriol by these cells. We found a significantly higher 1 alpha-OHase-expression in the placental tissue of pregnant women with preeclampsia or preterm birth compared to healthy pregnant women, whereas the expression of 25-OHase was significantly reduced. These results correlate with other studies and support the significance of the placenta regarding metabolism malfunctions as they were observed in the calcium metabolism for preeclampsia. That a placenta with preeclampsia expresses less 1 alpha-OHase-mRNA and shows less 1 alpha-OHase-activity than in placental samples of inconspicuous placentae, can be granted as a specific alteration in the placental ability to synthesize adequate amounts of 1,25(OH)2D3.