title: Iodine Affects Differentiation and Migration Process in Trophoblastic Cells.
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, supplementing low 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.
authors.affiliation: Centro de investigaciones Biomédicas, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa, Veracruz, México.|Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa, Veracruz, México.
authors.forename: Zendy Evelyn
authors.initials: ZE
authors.lastname: Olivo-Vidal
authors.affiliation: Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa, Veracruz, México.
authors.forename: Roció Coutiño
authors.initials: RC
authors.lastname: Rodríguez
authors.affiliation: Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa, Veracruz, México. elindirene@hotmail.com.
authors.forename: Omar
authors.initials: O
authors.lastname: Arroyo-Helguera
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007455:Iodine / Q000172:deficiency / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D007455:Iodine
keywords: HIF; Iodine deficiency; Oxidative stress; Placenta; Snail; Trophoblast; Trophoblasts