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The Placental Phenotype Adapts to Chronic Hypoxia and Mitochondria-Targeted Antioxidant (MitoQ) Therapy in Rat Pregnancy

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This is an author version of the contribution published on:

Reproductive Sciences, March 2016; vol. 23, 1 suppl: pp. 1A-50A, SAGE publications The Placental Phenotype Adapts to Chronic Hypoxia and Mitochondria-Targeted

Antioxidant (MitoQ) Therapy in Rat Pregnancy

Nuzzo AM 1,2, Camm EJ 1, Sferruzzi-Perri AN 1, Rolfo A 2, Todros T 2, Logan A3, Murphy MP3 & Giussani DA1

1 Department of Physiology, Development and Neuroscience, University of

Cambridge, United Kingdom;

2 Department of Surgical Sciences, University of Turin, Italy 3 MRC Mitochondrial Biology Unit, Cambridge, United Kingdom

Introduction: The placenta responds to adverse environmental conditions, such as maternal glucorticoid over-exposure and dietary manipulation, by adapting its capacity for substrate transfer to maintain appropriate fetal growth and development (Fowden et al. J Neuroendocrinol 20(4):439, 2008). Comparatively little is known about placental adaptations to hypoxia and/or oxidative stress. Here, we determined the effect of maternal chronic hypoxia on placental morphology and established whether maternal treatment with MitoQ protected against hypoxia-induced alterations in placental structure.

Methods: Wistar dams were exposed to normoxia (N, 21% O2) or hypoxia (H, 13% O2) from days 6-20 of pregnancy +/- MitoQ (500µM in drinking water). On day 20, animals were sacrificed and weighed and the placentae were processed for stereology. One placenta per litter per group was used. This model does not affect maternal food intake.

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Results: Neither hypoxic pregnancy or mitoQ treatment affected fetal growth (N: 3.6±0; H: 3.4±0; HM: 3.6±0; NM: 3.4±0 g). Relative to normoxia, the placental absolute volume and the labyrinthine fetal capillary surface area were significantly increased in hypoxic pregnancy (Fig. 1 A and B, P<0.05). Maternal MitoQ treatment in hypoxic pregnancy additionally increased the maternal blood space surface area (Fig. 1C, P<0.05).

Conclusions: The data show that the placenta adapts to chronic hypoxic pregnancy by increasing the fetal capillary surface within the labyrinthine transport zone to maintain fetal growth. Maternal mitochondrial targeted antioxidant therapy during hypoxic pregnancy improves perfusion on the maternal side of the placenta.

Supported by the British Heart Foundation

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