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Impact of vitamin D and vitamin D receptor on the trophoblast survival capacity in preeclampsia.

ABSTRACT: BACKGROUND:Preeclampsia and intra-uterine growth restriction (IUGR) are major health problems during pregnancy affecting both mother and child. Defective placental development and failure of trophoblast differentiation during pregnancy are important aspects in the pathogenesis of both syndromes. Recent studies have shown that autophagy is involved in the trophoblast survival capacity. As vitamin D has a central role in many cellular processes, we studied the relation of vitamin D and autophagy in those processes of preeclampsia and IUGR. METHODS:Serum and placental samples from four groups of cases; normal term, IUGR, early-onset and late-onset preeclampsia, were analyzed for 25(OH)D vitamin D, sFLT1, PGF, LGALS13 in serum and vitamin D receptor (VDR), MAP1LC3B and BECN1 in placental tissues. RESULTS:There was a significant difference in the sFLT1/PGF ratio in preeclamptic cases compared to controls and IUGR. There was a significant difference between these groups in the MAP1LC3B/BECN1 ratio as marker of the trophoblast survival capacity with a significantly reduced ratio in villous trophoblast of early-onset preeclampsia. Maternal vitamin D deficiency was found in all pathological pregnancies combined with significantly reduced staining levels of placental VDR in IUGR. Finally, there was a strong and significant negative correlation between the survival capacity (MAP1LC3B/BECN1) and both maternal vitamin D and placental VDR in the preeclampsia groups. CONCLUSION:Vitamin D and intracellular VDR are strongly related to the trophoblast survival capacity in preeclampsia.

SUBMITTER: Hutabarat M

PROVIDER: S-EPMC6226106 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Impact of vitamin D and vitamin D receptor on the trophoblast survival capacity in preeclampsia.

Hutabarat Martina M Wibowo Noroyono N Obermayer-Pietsch Barbara B Huppertz Berthold B

PloS one 20181108 11

<h4>Background</h4>Preeclampsia and intra-uterine growth restriction (IUGR) are major health problems during pregnancy affecting both mother and child. Defective placental development and failure of trophoblast differentiation during pregnancy are important aspects in the pathogenesis of both syndromes. Recent studies have shown that autophagy is involved in the trophoblast survival capacity. As vitamin D has a central role in many cellular processes, we studied the relation of vitamin D and aut ...[more]

PMID: 30408071

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Project description:Preeclampsia (PE) is a common cause of maternal morbidity, characterized by impaired trophoblast invasion and spiral artery transformation resulting in progressive uteroplacental hypoxia. Given the primary role of LIN28A and LIN28B in modulating cell metabolism, differentiation, and invasion, we hypothesized that LIN28A and/or LIN28B regulates trophoblast differentiation and invasion, and that its dysregulation may contribute to PE. Here we show that LIN28B is expressed ∼1300-fold higher than LIN28A in human term placenta and is the predominant paralog expressed in primary human trophoblast cultures. The expression of LIN28B mRNA and protein levels are significantly reduced in gestational age-matched preeclamptic vs. normal placentas, whereas LIN28A expression is not different. First trimester human placental sections displayed stronger LIN28B immunoreactivity in extravillous (invasive) cytotrophoblasts and syncytial sprouts vs. villous trophoblasts. LIN28B overexpression increased HTR8 cell proliferation, migration, and invasion, whereas LIN28B knockdown in JEG3 cells reduced cell proliferation. Moreover, LIN28B knockdown in JEG3 cells suppressed syncytin 1 (SYN-1), apelin receptor early endogenous ligand (ELABELA), and the chromosome 19 microRNA cluster, and increased mRNA expression of ITGβ4 and TNF-α. Incubation of BeWo and JEG3 cells under hypoxia significantly decreased expression of LIN28B and LIN28A, SYN-1, and ELABELA, whereas TNF-α is increased. These results provide the first evidence that LIN28B is the predominant paralog in human placenta and that decreased LIN28B may play a role in PE by reducing trophoblast invasion and syncytialization, and by promoting inflammation.-Canfield, J., Arlier, S., Mong, E. F., Lockhart, J., VanWye, J., Guzeloglu-Kayisli, O., Schatz, F., Magness, R. R., Lockwood, C. J., Tsibris, J. C. M., Kayisli, U. A., Totary-Jain, H. Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration.

Dataset Information

Impact of vitamin D and vitamin D receptor on the trophoblast survival capacity in preeclampsia.

Publications

Impact of vitamin D and vitamin D receptor on the trophoblast survival capacity in preeclampsia.

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