Lasting Effects of Low to Non-Lethal Radiation Exposure during Late Gestation on Offspring's Cardiac Metabolism and Oxidative Stress.

Ashley S Nemec-Bakk,Alain Simard,Shayenthiran Sreetharan,Neelam Khaper,Danika Roy,Lisa Stoa,Caitlund Davidson,Simon J Lees,T.C Tai,Joanna Y Wilson,Douglas R Boreham,Sarah Niccoli

doi:10.3390/antiox10050816

Ashley S Nemec-Bakk, Alain Simard + Show 10 more

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https://doi.org/10.3390/antiox10050816

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Abstract

Ionizing radiation (IR) is known to cause fetal programming, but the physiological effects of low-dose IR are not fully understood. This study examined the effect of low (50 mGy) to non-lethal (300 and 1000 mGy) radiation exposure during late gestation on cardiac metabolism and oxidative stress in adult offspring. Pregnant C57BL/6J mice were exposed to 50, 300, or 1000 mGy of gamma radiation or Sham irradiation on gestational day 15. Sixteen weeks after birth, 18F-Fluorodeoxyglucose (FDG) uptake was examined in the offspring using Positron Emission Tomography imaging. Western blot was used to determine changes in oxidative stress, antioxidants, and insulin signaling related proteins. Male and female offspring from irradiated dams had lower body weights when compared to the Sham. 1000 mGy female offspring demonstrated a significant increase in 18F-FDG uptake, glycogen content, and oxidative stress. 300 and 1000 mGy female mice exhibited increased superoxide dismutase activity, decreased glutathione peroxidase activity, and decreased reduced/oxidized glutathione ratio. We conclude that non-lethal radiation during late gestation can alter glucose uptake and increase oxidative stress in female offspring. These data provide evidence that low doses of IR during the third trimester are not harmful but higher, non-lethal doses can alter cardiac metabolism later in life and sex may have a role in fetal programming.

Highlights

An unfavorable fetal environment can affect growth and development of the fetus, and these changes can persist throughout life, which is commonly referred to as fetal programming
Female offspring in the 50, 300, and 1000 mGy groups had significantly reduced body weights compared to Sham group. 50 mGy female offspring heart weights were significantly lower than Sham, and 1000 mGy was significantly lower than Sham and 300 mGy groups (Table 1)
An adverse fetal environment can result in programming that causes developmental changes that can persist through to adulthood

Summary

Introduction

An unfavorable fetal environment can affect growth and development of the fetus, and these changes can persist throughout life, which is commonly referred to as fetal programming. Adverse fetal environment can result in changed placental morphology, low birth weight, and accelerated growth, which have been linked to many diseases later, including cardiovascular disease, cancer, diabetes mellitus, coronary heart disease, and hypertension [1,2,3,4,5]. Exposure to a variety of stressors during pregnancy can lead to low birth weight [6]. Stressors have the ability to activate the hypothalamic-pituitaryadrenal (HPA) axis [2,7]. Activation of the HPA axis can result in increased glucocorticoid production [2,7], which is known to cause insulin resistance and could result in altered cardiac glucose metabolism [8,9].

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