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

Lee, DC; Romero R.; Kim, JS; Tarca, AL; Montenegro D.; Pineles, BL; Kim E.; Lee, J; Kim, SY; Draghici, S; Mittal, P; Kusanovic, JP; Chaiworapongsa, T; Hassan, SS; Kim, CJ

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), preeclampsia (n = 52), 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 tniR-210 perturbing trophoblast iron metabolism is associated with defective placentation. (Am J Pathol 2011, 179:590-602; DOI: 10.1016/j.ajpath.2011.04.035)

Más información

Título según WOS: 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
Título de la Revista: AMERICAN JOURNAL OF PATHOLOGY
Volumen: 179
Número: 2
Editorial: Elsevier Science Inc.
Fecha de publicación: 2011
Página de inicio: 590
Página final: 602
Idioma: English
DOI:

10.1016/j.ajpath.2011.04.035

Notas: ISI