Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori 039-3212, Japan.
Radiat Res. 2018 Apr;189(4):425-440. doi: 10.1667/RR14863.1. Epub 2018 Feb 13.
Pregnant C57BL/6JJcl mice were exposed to γ rays at low dose rate (20 mGy/day, LDR) or medium dose rate (200 and 400 mGy/day, MDR) from gestation day (GD) 0-18 to total accumulated doses of 360, 3,600 and 7,200 mGy, respectively. An additional group of pregnant mice were acutely exposed to 2 Gy at high dose rate (HDR) of 0.77 Gy/min on GD 11. In experiment 1, fetuses collected via cesarean section on GD 18 were examined for external and skeletal abnormalities. While the results of LDR exposure (20 mGy/day) did not significantly differ from the nonirradiated controls in all parameters examined, MDR (200 and 400 mGy/day) and acute HDR (2 Gy) exposure caused growth retardation and significantly increased incidence of unossified bones. Increased incidence of external abnormalities was observed only in the acute HDR group. In experiment 2, the dams were allowed to give birth and the pups were clinically monitored and weighed periodically until 10 weeks of age when they were sacrificed and subjected to pathological examination. Pups exposed at MDRs of 200 and 400 mGy/dayand at acute HDR of 0.77 Gy/min had lower bodyweights from weaning (3 weeks) to 10 weeks of age except for females exposed to 400 mGy/day MDR. None of the pups exposed to an acute 2 Gy dose on GD 11 survived to 10 weeks of age. Histopathological changes were not significantly different between the nonirradiated control and the 20 mGy/day LDR groups. However, at both MDR exposures of 200 and 400 mGy/day. gonadal (testes and ovary) hypoplasia/atrophy was observed in all the 10-week-old pups. Our results show that in utero LDR exposure to 20 mGy/day for the entire gestation period did not cause any significant effect in pups when compared to the nonirradiated controls up to 10 weeks of age. However, pups exposed in utero to MDRs showed dose-related growth retardation with delayed ossifications (400 mGy/day) and gonadal hypoplasia/atrophy. These findings suggest that increased post-implantation loss in dams exposed at MDR is due to early embryonic deaths resulting in early resorption.
从受孕日(GD)0 到 18 日,将 C57BL/6JJcl 怀孕小鼠以低剂量率(20 mGy/天,LDR)或中剂量率(200 和 400 mGy/天,MDR)暴露于γ射线,分别接受总计 360、3600 和 7200 mGy 的累积剂量。另一组怀孕小鼠在 GD 11 时以高剂量率(0.77 Gy/min)急性接受 2 Gy 照射。在实验 1 中,通过剖宫产术收集 GD 18 的胎儿,检查其外部和骨骼异常。虽然 LDR 暴露(20 mGy/天)在所有检查参数中与未照射对照相比没有显著差异,但 MDR(200 和 400 mGy/天)和急性 HDR(2 Gy)暴露导致生长迟缓,并显著增加未骨化骨骼的发生率。仅在急性 HDR 组观察到外部异常发生率增加。在实验 2 中,允许母鼠分娩,并定期对幼崽进行临床监测和称重,直到 10 周龄时处死并进行病理检查。在 MDR 为 200 和 400 mGy/天和急性 HDR 为 0.77 Gy/min 暴露的幼崽中,除了接受 400 mGy/天 MDR 暴露的雌性幼崽外,从断奶(3 周)到 10 周龄的体重均较低。在 GD 11 接受急性 2 Gy 剂量照射的幼崽无一存活至 10 周龄。与未照射对照组和 20 mGy/天 LDR 组相比,非照射对照组和 20 mGy/天 LDR 组之间的组织病理学变化无显著差异。然而,在 MDR 为 200 和 400 mGy/天的两种暴露中,所有 10 周龄的幼崽均观察到性腺(睾丸和卵巢)发育不良/萎缩。我们的结果表明,在整个妊娠期以 20 mGy/天的 LDR 宫内暴露与未照射对照相比,在 10 周龄之前对幼崽没有造成任何显著影响。然而,在宫内接受 MDR 暴露的幼崽表现出与剂量相关的生长迟缓,伴有骨化延迟(400 mGy/天)和性腺发育不良/萎缩。这些发现表明,MDR 暴露的母鼠中着床后损失增加是由于早期胚胎死亡导致早期吸收。