Botting-Lawford, Kimberley J;
Skeffington, Katie L;
Murphy, Michael P;
David, Anna L;
Giussani, Dino A;
(2025)
Antioxidants: powering the fight against fetal hypoxia.
Philosophical Transactions of the Royal Society B: Biological Sciences
, 380
(1933)
, Article 20240183. 10.1098/rstb.2024.0183.
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Abstract
Hypoxia is a common challenge in fetal development. Short-term acute episodes occur during labour owing to uterine contractions or umbilical cord compression. In response, the fetus prioritizes oxygen and nutrient delivery to the brain, heart and adrenal glands at the expense of other organs, a mechanism known as the fetal brain-sparing response. However, prolonged fetal hypoxia can occur in many conditions, including placental insufficiency, pre-eclampsia, high-altitude pregnancy and fetal congenital heart disease. Chronic hypoxia increases placental and fetal oxidative stress, triggering increased long-term cardiovascular risks in adult offspring, including hypertension and coronary artery disease. Antioxidants could potentially prevent this. However, as reactive oxygen species play a crucial role in the fetal brain-sparing response, excessive antioxidant use could weaken fetal defences against acute hypoxia, increasing the risk of hypoxic-ischaemic encephalopathy. Thus, for clinical use, an antioxidant should protect against programmed cardiovascular disease while preserving fetal brain sparing. This review summarizes preclinical evidence on the efficacy of antioxidants in preventing cardiovascular disease in the offspring of hypoxic pregnancy. We compare their effects on fetal brain sparing, highlighting the ability of the mitochondria-targeted antioxidant MitoQ to protect against programmed cardiovascular disease while preserving fetal brain sparing and outlining steps for clinical translation. This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.
| Type: | Article |
|---|---|
| Title: | Antioxidants: powering the fight against fetal hypoxia |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1098/rstb.2024.0183 |
| Publisher version: | https://doi.org/10.1098/rstb.2024.0183 |
| Language: | English |
| Additional information: | © 2025 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
| Keywords: | Hypoxia, high altitude, fetal growth restriction, antioxidant, MitoQ, clinical translation, pregnancy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10213106 |
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