Preeclampsia is associated with first trimester placental dysfunction. miR-210, a
small non-coding RNA, is increased in the preeclamptic placenta. The effects of elevated
miR-210 on placental function remain unclear. The objectives of this study were to
identify targets of miR-210 in first trimester primary extravillous trophoblasts (EVTs)
and to investigate functional pathways altered by elevated placental miR-210 during
early pregnancy. EVTs isolated from first trimester placentas were exposed to cobalt
chloride (CoCl2), a HIF-1 alpha stabilizer and hypoxia mimetic, and miR-210 expression
by qPCR, HIF1 alpha protein levels by western blot and cell invasion were assessed.
A custom TruSeq RNA array, including all known/predicted miR-210 targets, was run
using miR-210 and miR-negative control transfected EVTs. Mitochondrial function was
assessed by high resolution respirometry in transfected EVTs. EVTs exposed to CoCl2
showed a dose and time-dependent increase in miR-210 and HIF1 alpha and reductions
in cell invasion. The TruSeq array identified 49 altered genes in miR-210 transfected
EVTs with 27 genes repressed and 22 enhanced. Three of the top six significantly repressed
genes, NDUFA4, SDHD, and ISCU, are associated with mitochondrial function. miR-210
transfected EVTs had decreased maximal, complex II and complex I+II mitochondrial
respiration. This study suggests that miR-210 alters first trimester trophoblast function.
miR-210 overexpression alters EVT mitochondrial function in early pregnancy. Mitochondrial
dysfunction may lead to increased reactive oxygen species, trophoblast cell damage
and likely contributes to the pathogenesis of preeclampsia.