Expression and Activity of 25-Hydroxyvitamin D-1 -Hydroxylase Are Restricted in Cultures of Human Syncytiotrophoblast Cells from Preeclamptic Pregnancies

Dı́az, Lorenza

doi:10.1210/jc.87.8.3876

Cited by 61 publications

(78 citation statements)

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“…Altered mRNA expressions for CYP27B1, CYP24A1, or VDR were previously reported to be either increased or decreased in preeclamptic placentas compared with normal placentas (11,13). In our study, we determined the distributions and expressions of major vitamin D metabolic components, including VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR, by immunostaining and by Western blot analysis in placental tissues from normal and preeclamptic pregnancies.…”

Section: Discussionmentioning

confidence: 97%

Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies

Zhao

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

135

108

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Vitamin D insufficiency/deficiency during pregnancy has been linked to increased risk of preeclampsia. Placenta dysfunction plays an important role in the pathogenesis of this pregnancy disorder. In this study, we tested the hypothesis that disturbed vitamin D metabolism takes place in preeclamptic placentas. Protein expressions of vitamin D binding protein (VDBP), 25-hydroxylase (CYP2R1), 1␣-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D receptor (VDR) were examined in placentas from normotensive and preeclamptic pregnancies. By immunostaining we found that in normal placenta VDBP, CYP24A1, and VDR expressions are localized mainly in trophoblasts, whereas CYP2R1 and CYP27B1 expressions are localized mainly in villous core fetal vessel endothelium. Protein expressions of CYP2R1 and VDR are reduced, but CYP27B1 and CYP24A1 expressions are elevated, in preeclamptic compared with normotensive placentas. Because increased oxidative stress is an underlying pathophysiology in placental trophoblasts in preeclampsia, we further determined whether oxidative stress contributes to altered vitamin D metabolic system in placental trophoblasts. Trophoblasts isolated from normal-term placentas were treated with hypoxic-inducing agent CoCl 2, and protein expressions of VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR were determined. We found that hypoxia-induced downregulation of VDBP, CYP2R1, and VDR and upregulation of CYP27B1 and CYP24A1 expressions were consistent with that seen in preeclamptic placentas. CuZnSOD expression was also downregulated in trophoblasts treated with CoCl 2. These results provide direct evidence of disrupted vitamin D metabolic homeostasis in the preeclamptic placenta and suggest that increased oxidative stress could be a causative factor of altered vitamin D metabolism in preeclamptic placentas. Vitamin D status during pregnancy has been drawing great attention (19,22,32,39). Studies have shown that sufficient vitamin D intake during pregnancy reduces the risk of complications, including gestational diabetes, preterm birth, and infection (8, 36). Conversely, vitamin D deficiency during pregnancy has been linked to several adverse pregnancy outcomes (19,22,32,39), including those associated with placental insufficiency such as preeclampsia and low birth weight (8,36). Maternal 25(OH)D 3 levels are lower in women with preeclampsia than in normotensive pregnant women (1, 7). Moreover, a nested case control study revealed that maternal vitamin D deficiency at less than 22 wk of gestation is a strong, independent risk factor for preeclampsia (7). The finding of the association of maternal vitamin D deficiency and increased risk of preeclampsia (3,7,28,29) further emphasizes the importance of adequate vitamin D levels and proper vitamin D metabolism during pregnancy.Normal placental development and function ensure a healthy pregnancy outcome. It is believed that during pregnancy, 1,25(OH) 2 D 3 may be produced not only by kidneys but also by placenta trophoblasts. Human placenta and decidua are c...

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Section: Discussionmentioning

confidence: 97%

Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies

Zhao

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

135

108

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“…Cytotrophoblasts were isolated and cultured as described (18,19). Villous tissue was enzymatically dispersed; cytotrophoblasts were separated on a Percoll gradient, plated in DMEM-HG with 20% fetal bovine serum (FBS) and incubated at 37jC (95% humidity and 5% CO 2 atmosphere).…”

Section: Methodsmentioning

confidence: 99%

Estrogens and Human Papilloma Virus Oncogenes Regulate Human Ether-à-go-go-1 Potassium Channel Expression

Díaz¹,

Ceja-Ochoa

Restrepo-Angulo³

et al. 2009

Cancer Research

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Ether-à-go-go-1 (Eag1) potassium channels are potential tools for detection and therapy of numerous cancers. Here, we show human Eag1 (hEag1) regulation by cancer-associated factors. We studied hEag1 gene expression and its regulation by estradiol, antiestrogens, and human papillomavirus (HPV) oncogenes (E6/E7). Primary cultures from normal placentas and cervical cancer tissues; tumor cell lines from cervix, choriocarcinoma, keratinocytes, and lung; and normal cell lines from vascular endothelium, keratinocytes, and lung were used. Reverse transcription-PCR (RT-PCR) experiments and Southern blot analysis showed Eag1 expression in all of the cancer cell types, normal trophoblasts, and vascular endothelium, in contrast to normal keratinocytes and lung cells. Estradiol and antiestrogens regulated Eag1 in a cell type-dependent manner. Real-time RT-PCR experiments in HeLa cells showed that Eag1 estrogenic regulation was strongly associated with the expression of estrogen receptor-A. Eag1 protein was detected by monoclonal antibodies in normal placenta and placental blood vessels. Patch-clamp recordings in normal trophoblasts treated with estradiol exhibited potassium currents resembling Eag1 channel activity. Eag1 gene expression in keratinocytes depended either on cellular immortalization or the presence of HPV oncogenes. Eag1 protein was found in keratinocytes transfected with E6/E7 HPV oncogenes. Cell proliferation of E6/E7 keratinocytes was decreased by Eag1 antibodies inhibiting channel activity and by the nonspecific Eag1 inhibitors imipramine and astemizole; the latter also increased apoptosis. Our results propose novel oncogenic mechanisms of estrogen/ antiestrogen use and HPV infection. We also suggest Eag1 as an early indicator of cell proliferation leading to malignancies and a therapeutic target at early stages of cellular hyperproliferation. [Cancer Res 2009;69(8):3300-7]

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“…Another study found that serum levels of the fat-soluble vitamins A, D, and E were each lower in preeclamptic women compared with normotensive pregnant and nonpregnant controls (485), which raises the possibility that confounding from overweight, obesity, and poor nutrition may explain why the levels of several fatsoluble vitamins were all lowered in preeclamptic women. A placental abnormality has been hypothesized to explain lower calcitriol levels in preeclampsia, with conflicting results obtained showing decreased (248) and increased (286) placental expression of Cyp27b1. However, since the placenta contributes very little calcitriol to the circulation of pregnant women (see sect.…”

Section: Human Datamentioning

confidence: 99%

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

Kovacs

2016

Physiological Reviews

383

524

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During pregnancy and lactation, female physiology adapts to meet the added nutritional demands of fetuses and neonates. An average full-term fetus contains ϳ30 g calcium, 20 g phosphorus, and 0.8 g magnesium. About 80% of mineral is accreted during the third trimester; calcium transfers at 300-350 mg/day during the final 6 wk. The neonate requires 200 mg calcium daily from milk during the first 6 mo, and 120 mg calcium from milk during the second 6 mo (additional calcium comes from solid foods). Calcium transfers can be more than double and triple these values, respectively, in women who nurse twins and triplets. About 25% of dietary calcium is normally absorbed in healthy adults. Average maternal calcium intakes in American and Canadian women are insufficient to meet the fetal and neonatal calcium requirements if normal efficiency of intestinal calcium absorption is relied upon. However, several adaptations are invoked to meet the fetal and neonatal demands for mineral without requiring increased intakes by the mother. During pregnancy the efficiency of intestinal calcium absorption doubles, whereas during lactation the maternal skeleton is resorbed to provide calcium for milk. This review addresses our current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery. Also considered are the impacts that these adaptations have on biochemical and hormonal parameters of mineral homeostasis, the consequences for long-term skeletal health, and the presentation and management of disorders of mineral and bone metabolism.

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Expression and Activity of 25-Hydroxyvitamin D-1 -Hydroxylase Are Restricted in Cultures of Human Syncytiotrophoblast Cells from Preeclamptic Pregnancies

Cited by 61 publications

References 0 publications

Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies

Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies

Estrogens and Human Papilloma Virus Oncogenes Regulate Human Ether-à-go-go-1 Potassium Channel Expression

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

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