Placental Adaptation to Early-Onset Hypoxic Pregnancy and Mitochondria-Targeted Antioxidant Therapy in a Rodent Model.

TitlePlacental Adaptation to Early-Onset Hypoxic Pregnancy and Mitochondria-Targeted Antioxidant Therapy in a Rodent Model.
Publication TypeJournal Article
Year of Publication2018
AuthorsNuzzo, AM, Camm, EJ, Sferruzzi-Perri, AN, Ashmore, TJ, Yung, H-W, Cindrova-Davies, T, Spiroski, A-M, Sutherland, MR, Logan, A, Austin-Williams, S, Burton, GJ, Rolfo, A, Todros, T, Murphy, MP, Giussani, DA
JournalAm J Pathol
Volume188
Issue12
Pagination2704-2716
Date Published2018 Dec
ISSN1525-2191
Abstract

The placenta responds to adverse environmental conditions by adapting its capacity for substrate transfer to maintain fetal growth and development. Early-onset hypoxia effects on placental morphology and activation of the unfolded protein response (UPR) were determined using an established rat model in which fetal growth restriction is minimized. We further established whether maternal treatment with a mitochondria-targeted antioxidant (MitoQ) confers protection during hypoxic pregnancy. Wistar dams were exposed to normoxia (21% O) or hypoxia (13% to 14% O) from days 6 to 20 of pregnancy with and without MitoQ treatment (500 μmol/L in drinking water). On day 20, animals were euthanized and weighed, and the placentas from male fetuses were processed for stereology to assess morphology. UPR activation in additional cohorts of frozen placentas was determined with Western blot analysis. Neither hypoxic pregnancy nor MitoQ treatment affected fetal growth. Hypoxia increased placental volume and the fetal capillary surface area and induced mitochondrial stress as well as the UPR, as evidenced by glucose-regulated protein 78 and activating transcription factor (ATF) 4 protein up-regulation. MitoQ treatment in hypoxic pregnancy increased placental maternal blood space surface area and volume and prevented the activation of mitochondrial stress and the ATF4 pathway. The data suggest that mitochondria-targeted antioxidants may be beneficial in complicated pregnancy via mechanisms protecting against placental stress and enhancing placental perfusion.

DOI10.1016/j.ajpath.2018.07.027
Alternate JournalAm. J. Pathol.
Citation Key10.1016/j.ajpath.2018.07.027
PubMed ID30248337
PubMed Central IDPMC6284551
Grant List / / Wellcome Trust / United Kingdom
MC_U105663142 / / Medical Research Council / United Kingdom
PG/14/5/30547 / / British Heart Foundation / United Kingdom