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- Title
Chronically Hypoxic Fetal Lambs Supported by an Extra-Uterine Device Exhibit Mitochondrial Dysfunction and Elevations of Hypoxia Inducible Factor 1-Alpha.
- Authors
Rossidis, Avery C.; Baumgarten, Heron D.; Lawrence, Kendall M.; McGovern, Patrick E.; Mejaddam, Ali Y.; Li, Haiying; Hwang, Grace; Young, Kathleen; Peranteau, William H.; Davey, Marcus G.; Gaynor, J. William; Flake, Alan W.; Rossidis, Avery C; Baumgarten, Heron D; Lawrence, Kendall M; McGovern, Patrick E; Mejaddam, Ali Y; Peranteau, William H; Davey, Marcus G; Gaynor, J William
- Abstract
<bold>Introduction: </bold>We have recently developed an extra-uterine environment for neonatal development (EXTEND) capable of supporting premature fetal lambs and have been able to replicate hypoxic in utero conditions by controlling fetal oxygen delivery. In this study, we investigated the fetal mitochondrial response to hypoxia.<bold>Methods: </bold>Eight premature fetal lambs were delivered via hysterotomy and transitioned to extra-uterine support for 3 weeks. The lambs were divided into 2 groups: normoxic fetuses which maintained physiologic oxygen delivery and hypoxic fetuses in which oxygen delivery was significantly reduced. Control fetuses were delivered via hysterotomy but not cannulated. Measurements of mitochondrial membrane potential (MMP) were performed in peripheral blood mononuclear cells.<bold>Results: </bold>There were no significant differences in MMP between normoxic EXTEND fetuses and controls. Hypoxic fetuses had significantly more depolarized mitochondria compared to normoxic fetuses overall, and these changes were specifically appreciated in weeks 1 and 2, but not by week 3. Hypoxic fetuses had significantly elevated levels of HIF-1α compared to normoxic fetuses in the first 2 weeks.<bold>Discussion: </bold>Normoxic fetal lambs supported by EXTEND demonstrate normal mitochondrial function as evidenced by equivalent membrane potentials compared to control fetuses. Hypoxic fetuses exhibit mitochondrial dysfunction, though they do show evidence of adaptation after 3 weeks of hypoxic exposure.
- Subjects
MITOCHONDRIAL pathology; MEMBRANE potential measurement; FETAL anoxia; FETAL development; PHYSIOLOGICAL transport of oxygen; ANIMALS; BIOLOGICAL transport; FETAL malnutrition; PROTEINS; SHEEP
- Publication
Fetal Diagnosis & Therapy, 2019, Vol 45, Issue 3, p176
- ISSN
1015-3837
- Publication type
journal article
- DOI
10.1159/000488283