MiR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: Siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies

Deug Chan Lee, Roberto Romero, Jung Sun Kim, Adi L. Tarca, Daniel Montenegro, Beth L. Pineles, Ernest Kim, Joonho Lee, Sun Young Kim, Sorin Draghici, Pooja Mittal, Juan Pedro Kusanovic, Tinnakorn Chaiworapongsa, Sonia S. Hassan, Chong Jai Kim

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Abstract

This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), ii) preeclampsia (n = 52), iii) SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O 2) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3′ UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3′ UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation.

Original languageEnglish
Pages (from-to)590-602
Number of pages13
JournalAmerican Journal of Pathology
Volume179
Issue number2
DOIs
Publication statusPublished - 2011 Aug 1

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All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Lee, D. C., Romero, R., Kim, J. S., Tarca, A. L., Montenegro, D., Pineles, B. L., Kim, E., Lee, J., Kim, S. Y., Draghici, S., Mittal, P., Kusanovic, J. P., Chaiworapongsa, T., Hassan, S. S., & Kim, C. J. (2011). MiR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: Siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies. American Journal of Pathology, 179(2), 590-602. https://doi.org/10.1016/j.ajpath.2011.04.035