Chronic hypoxia in ovine pregnancy recapitulates physiological and molecular markers of preeclampsia in the mother, placenta and offspring
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Authors
Tong, Wen
Allison, Beth
Brain, Kirsty
Patey, Olga
Niu, Youguo
Botting, Kimberley
Ford, Sage
Garrud, Tessa
Shaw, Caroline
Lyu, Qiang
Zhang, Lin
Ma, Jin
Cindrova-Davies, Tereza
Yung, Hong Wa
Publication Date
2022-07Journal Title
Hypertension
ISSN
0194-911X
Publisher
American Heart Association
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Tong, W., Allison, B., Brain, K., Patey, O., Niu, Y., Botting, K., Ford, S., et al. (2022). Chronic hypoxia in ovine pregnancy recapitulates physiological and molecular markers of preeclampsia in the mother, placenta and offspring. Hypertension https://doi.org/10.1161/HYPERTENSIONAHA.122.19175
Abstract
Background: Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast to the impact of hypoxia on the placenta and fetus, comparatively little is known on the maternal physiology.
Methods: We adopted an integrative approach to investigate the inter-relationship between chronic hypoxia during pregnancy with maternal, placental and fetal outcomes, common in preeclampsia. We exploited a novel technique using isobaric hypoxic chambers and in vivo continuous cardiovascular recording technology for measurement of blood pressure in sheep and studied the placental stress in response to hypoxia at cellular and sub-cellular levels.
Results: Chronic hypoxia in ovine pregnancy promoted fetal growth restriction with evidence of fetal brain-sparing, increased placental hypoxia-mediated oxidative damage and activated placental stress response pathways. These changes were linked with dilation of the placental endoplasmic reticulum cisternae and increased placental expression of the antiangiogenic factors sFlt-1 and sEng, combined with a shift towards an angiogenic imbalance in the maternal circulation. Chronic hypoxia further led to an increase in uteroplacental vascular resistance, and the fall in maternal blood pressure with advancing gestation measured in normoxic pregnancy did not occur in hypoxic pregnancy.
Conclusions: Therefore, we show in an ovine model of sea level adverse pregnancy that chronic hypoxia recapitulates physiological and molecular features of preeclampsia in the mother, placenta and offspring.
Sponsorship
British Heart Foundation (RG/17/8/32924)
British Heart Foundation (None)
Identifiers
External DOI: https://doi.org/10.1161/HYPERTENSIONAHA.122.19175
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336635
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