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Behavioral changes and structural defects in rats irradiated in utero
1Department of Radiation Oncology, University of Kansas Medical Center, Kansas City 66103.
Insights
Low-dose in utero irradiation during pregnancy can cause functional and morphological deficits in offspring. The timing of radiation exposure is critical, with the developing brain showing peak sensitivity around gestational day 15.
Area of Science:
- Developmental Biology
- Radiation Biology
- Neuroscience
Background:
- Prenatal exposure to ionizing radiation is a concern for fetal development.
- Understanding the sensitivity of the developing fetus to radiation is crucial for risk assessment.
Purpose of the Study:
- To investigate the effects of in utero gamma-ray irradiation on postnatal development and behavior in rats.
- To determine the critical window of radiation sensitivity during gestation.
Main Methods:
- Pregnant rats were exposed to Cesium-137 gamma-rays at various doses and gestational days.
- Offspring were assessed for preweaning behaviors, body weight, and tissue morphology (brain and pituitary).
Main Results:
- Dose-dependent changes in behavior were observed, with some effects seen at low doses (0.25 Gy).
- The developing brain, particularly the sensorimotor cortex, showed increased sensitivity to radiation later in gestation (days 13-17), peaking on day 15.
- Pituitary sensitivity was higher earlier in gestation (day 11).
Conclusions:
- In utero irradiation, even at low doses, can lead to a range of functional and morphological deficits.
- The specific day of gestation significantly influences the type and severity of radiation-induced effects.
- Minimizing fetal exposure to radiation is recommended, even after early organogenesis.
Abstract:
Pregnant rats were irradiated with whole-body doses (0.25-1.25 Gy) of Cs-137 gamma-rays on gestational day 15, or with 1.0 Gy on gestational days 11, 13, 15, or 17. Postnatal growth (body weight) and several preweaning behaviors (righting reflex, negative geotaxis, reflex suspension, modified open field activity, spatial maze exploration, continuous corridor activity, and gait) of the offspring were monitored prior to sacrifice on post-parturition day 28. Brain (sensorimotor cortex) and pituitary tissues were processed for histological evaluation and morphometric analysis. For most behavioral endpoints, there were dose-dependent changes produced by irradiation on gestational day 15, with one endpoint (continuous corridor activity) demonstrating changes after 0.25 Gy that were significantly different from control values. The data indicate that the most sensitive organ showing radiation-induced alterations changes from the pituitary at gestational day 11 to the primitive cortex of the brain at days 13 to 17 with a peak of sensitivity at day 15. These results demonstrate that a spectrum of related functional and morphological deficits can be produced by even low-dose in utero irradiation, with the specific endpoint showing the greatest change being determined by the specific day of gestation on which irradiation occurs. Extrapolating from these experimental data with rats to the human situation, it is recommended that care be taken, when possible, to avoid exposure of the fetus, even after the early stages of organogenesis.