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Iodine Affects Differentiation and Migration Process in Trophoblastic Cells

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Abstract

Iodine deficiency is associated with oxidative stress increase and preeclampsia during gestation, suggesting that iodine concentration plays an important role in the normal placenta physiology. The question raised is to analyze the effect of iodine deficiency on oxidative stress, viability, differentiation, and migration process and changes in the expression of differentiation and migration markers. Iodine deprivation was done using potassium perchlorate (KCLO4) to block sodium iodide symporter (NIS) transporter and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid DIDS to inhibit pendrine (PEN) transport for 3–48 h. Then trophoblast cells were treated with low iodine doses of 5–500 μM and high iodine doses of 100–5000 μM. Oxidative stress, viability, and human chorionic gonadotropin (hGC) were measured by colorimetric methods. Migration throphoblast cells were evaluated by both wound healing and Boyden chamber assays. Changes in mRNA expression were analyzed by real-time RT-PCR. Iodine deprivation induces a significant increase of reactive oxygen species (ROS), viability, and migration process vs control cells. We found a significant overregulation in the mRNA’s peroxisome proliferator-activated receptor (PPAR-gamma), Snail, and matrix metalloproteinase-9 (MMP-9) mRNA’s in cells deprived of iodine, as well as a down glial cell missing-1 (GCM-1) regulation, hGC, pregnancy-associated plasma protein-A (PAPP-A), and E-cadherin mRNA expression. The expression of hypoxic induction factor alpha (HIFα) mRNA does not change with iodine deprivation. In cells deprived of iodine, supplementinglow iodine doses (5–500 μM) does not induce any significant changes in viability. However, ROS and migration process were decreased, although we found an increased human chorionic gonadotropin (hCG) secretion as a differentiation marker. In addition, we found that PPAR-gamma, Snail, and MPP-9 mRNAs expression are downregulated with low iodine doses, in contrast with GCM-1, PAPP-A, hGC, and E-cadherin that increase their expression vs cells deprived of iodine. High iodine doses (1000–5000 μM) have shown cytotoxic effects. Based on our results, iodine is important for keeping the proliferation/differentiation balance in the placenta.

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Acknowledgments

This study had financial support from Public Health Institute POA 2013-2015, SIREI 36941-201360, and CONACyT grant no. CB-2012-01-176513. The authors also wish to thank Irene Xochihua Rosas for proofreading. Zendy Evelyn Olivo-Vidal, a Biomedical Science PhD student, was supported by graduate fellowships from CONACyT 376830.

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Authors and Affiliations

  1. Centro de investigaciones Biomédicas, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa, Veracruz, México

    Zendy Evelyn Olivo-Vidal

  2. Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa, Veracruz, México

    Zendy Evelyn Olivo-Vidal, Roció Coutiño Rodríguez & Omar Arroyo-Helguera

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  1. Zendy Evelyn Olivo-Vidal
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  2. Roció Coutiño Rodríguez
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  3. Omar Arroyo-Helguera
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Correspondence to Omar Arroyo-Helguera.

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Olivo-Vidal, Z.E., Rodríguez, R.C. & Arroyo-Helguera, O. Iodine Affects Differentiation and Migration Process in Trophoblastic Cells. Biol Trace Elem Res 169, 180–188 (2016). https://doi.org/10.1007/s12011-015-0433-1

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