Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease

Stimulatory effects of calcitriol on hCG secretion and gene expression in cultured syncytiotrophoblasts

<p><b>Copyright information:</b></p><p>Taken from "Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts"</p><p>Reproductive biology and endocrinology : RB&E 2008;6():3-3.</p><p>Published online 22 Jan 2008</p><p>PMCID:PMC2245969.</p><p></p> A) Hormone secretion was determined by EIA after 6 hours incubation in the presence of increasing concentrations of calcitriol or its vehicle (-). B) Real time PCR analysis of hCGβ gene expression of calcitriol-treated cells. Results were normalized against GAPDH mRNA. Vehicle data were arbitrarily given a value of 1. Each bar represents the mean ± S.D. of triplicate cultures. *< 0.05 vs. control

Temporal pattern of hCG secretion (A) and expression (B) in cultured human trophoblasts

<p><b>Copyright information:</b></p><p>Taken from "Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts"</p><p>http://www.rbej.com/content/6/1/3</p><p>Reproductive biology and endocrinology : RB&E 2008;6():3-3.</p><p>Published online 22 Jan 2008</p><p>PMCID:PMC2245969.</p><p></p> Cytotrophoblasts were plated in the absence (●) or presence (▲) of 8-Br-cAMP (1.5 mM). Two scale bars were used in order to show all data [stimulated (▲) vs. non stimulated (●)] in the same graphic. Media was changed every day. A) Secretion of hCG in culture media was measured daily and results were expressed as mIU/mg protein. B) Real time PCR analysis of hCGβ expression in different culture days. Results were normalized against GAPDH mRNA. Vehicle data were arbitrarily given a value of 1. Basal hCG secretion and expression increased significantly compared with day 1. Note that hCGβ mRNA increased considerably on day 2 in the presence of 8-Br-cAMP (B), which was reflected on hCG secretion on day 3 (A), showing an important protein synthesis activity between day 2 and 3 of the cell culture. Data are presented as the mean ± S.D. of three different cell cultures. *< 0.05 vs. day 1; **< 0.05 vs. control