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A previous study demonstrated a causal role of microRNA\u2010210 (miR\u2010210) in gestational hypoxia\u2010induced suppression of Ca<jats:sup>2+<\/jats:sup> sparks\/spontaneous transient outward currents (STOCs) in ovine uterine arteries, but the underlying mechanisms remain undetermined. We tested the hypothesis that miR\u2010210 perturbs mitochondrial metabolism and increases mitochondrial reactive oxygen species (mtROS) that confer hypoxia\u2010induced suppression of STOCs in uterine arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Resistance\u2010sized uterine arteries were isolated from near\u2010term pregnant sheep and were treated <jats:italic>ex vivo<\/jats:italic> in normoxia and hypoxia (10.5% O<jats:sub>2<\/jats:sub>) for 48\u2009h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Hypoxia increased mtROS and suppressed mitochondrial respiration in uterine arteries, which were also produced by miR\u2010210 mimic to normoxic arteries and blocked by antagomir miR\u2010210\u2010LNA in hypoxic arteries. Hypoxia or miR\u2010210 mimic inhibited Ca<jats:sup>2+<\/jats:sup> sparks\/STOCs and increased uterine arterial myogenic tone, which were inhibited by the mitochondria\u2010targeted antioxidant MitoQ. Hypoxia and miR\u2010210 down\u2010regulated iron\u2013sulfur cluster scaffold protein (ISCU) in uterine arteries and knockdown of ISCU via siRNAs suppressed mitochondrial respiration, increased mtROS, and inhibited STOCs. In addition, blockade of mitochondrial electron transport chain with antimycin and rotenone inhibited large\u2010conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels, decreased STOCs and increased uterine arterial myogenic tone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>This study demonstrates a novel mechanistic role for the miR\u2010210\u2010ISCU\u2010mtROS axis in inhibiting Ca<jats:sup>2+<\/jats:sup> sparks\/STOCs in the maladaptation of uterine arteries and provides new insights into the understanding of mitochondrial perturbations in the pathogenesis of pregnancy complications resulted from hypoxia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15914","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T16:04:20Z","timestamp":1656691460000},"page":"4640-4654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["MicroRNA\u2010210\u2010mediated mtROS confer hypoxia\u2010induced suppression of STOCs in ovine uterine arteries"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1626-9541","authenticated-orcid":false,"given":"Xiang\u2010Qun","family":"Hu","sequence":"first","affiliation":[{"name":"Lawrence D. Longo MD Center for Perinatal Biology, Department of Basic Sciences Loma Linda University School of Medicine  Loma Linda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Song","sequence":"additional","affiliation":[{"name":"Lawrence D. Longo MD Center for Perinatal Biology, Department of Basic Sciences Loma Linda University School of Medicine  Loma Linda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiranjib","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Lawrence D. Longo MD Center for Perinatal Biology, Department of Basic Sciences Loma Linda University School of Medicine  Loma Linda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Romero","sequence":"additional","affiliation":[{"name":"Lawrence D. 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