Cardiovascular and growth outcomes of C57Bl/6J mice offspring exposed to maternal stress and ionizing radiation during pregnancy.

Purpose: Developmental programming involves an adverse intrauterine environment which can result in offspring phenotype changes following birth. The developmental programming of hypertension has been reported to possibly involve oxidative stress at the cellular level. Ionizing radiation produces oxidative stress, even at low doses, and irradiation of animals is often coupled with potential sources of maternal stress such as transportation of animals or repeated handling. Materials and methods: Pregnant C57Bl/6J mice were irradiated on gestational day 15 with 5-1000 mGy 137Cs gamma radiation. Post-natal weight, blood pressure (BP) and heart rate (HR) were measured. Radiation had minimal effects at doses ≤300 mGy, but 1000 mGy caused a significant reduction in HR in male pups and growth reduction at 16 weeks of age in both genders. The sham-irradiation protocol included repeated transportation in order to acclimate animals to transport. However, it may have resulted in programming, as sham-irradiation alone resulted in elevated BP measures compared to the offspring of animals that were never transported. Results and conclusions: Overall, there were minimal effects on cardiovascular measures or offspring weight due to irradiation except at 1000 mGy. The presence of maternal stress, a known trigger of developmental programming, may have confounded any potential irradiation effects.

Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease.

Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (<100 mGy) and oxidative stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

Ionizing Radiation Exposure During Pregnancy: Effects on Postnatal Development and Life.

Reliable human data on the effects of prenatal exposure to ionizing radiation are largely based on high-dose exposures. Exposure to low doses may produce effects that are not easily observable at birth, and may persist over the course of the offspring's postnatal life. This is important when considering fetal programing, a phenomenon characterized by changes in offspring phenotype due to a stress experienced in utero. In this review, we briefly summarize the known effects of both high- and low-dose exposure to ionizing radiation during pregnancy in humans. There is a major consensus that the atomic bomb survivors' data shows increased incidence of microcephaly and reductions in IQ of A-bomb survivors, whereas, with diagnostic radiography in utero there is no conclusive evidence of increased cancer risk. Due to the relatively limited data (particularly for low-dose exposures) in humans, animal models have emerged as an important tool to study prenatal effects of radiation. These animal models enable researchers to manipulate various experimental parameters and make it possible to analyze a wider variety of end points. In this review, we discuss the major findings from studies using mouse and rat models to examine prenatal ionizing radiation effects in postnatal development of the offspring. In addition, we broadly categorize trends across studies within three major stages of development: pre-implantation, organogenesis and fetal development. Overall, long-term effects of prenatal radiation exposure (including the possible role on the developmental programing of disease) are important factors to consider when assessing radiation risk, since these effects are of relevance even in the low-dose range.