Heat shock during rat embryo development in vitro results in decreased mitosis and abundant cell death
Heat shock during rat embryo development in vitro results in decreased mitosis and abundant cell death
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DOI：
10.1016/s0890-6238(98)00056-2
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发表时间：
1999-01-01
影响因子：
3.3
通讯作者：
Kimmel, CA
中科院分区：
文献类型：
--
作者：
Breen, JG;Claggett, TW;Kimmel, CA
流行病学研究强烈表明，在子宫内暴露于高温会导致人类的发育缺陷。大鼠、小鼠、豚鼠和暴露于高温的其他物种也表现出各种发育缺陷。我们实验室的研究主要集中在妊娠第10天（GD）大鼠体内或体外暴露于高温。在体内或体外暴露后24小时内，可观察到CNS、视杯、体节和肢体发育延迟或异常。出生时，GD 10高热后仅观察到肋骨和脊椎畸形，这些畸形已被证明是由于体节分割的改变。不分节的体节被认为是由减数分裂前中胚层的细胞周期阻滞引起的，体节在正常发育过程中单独出现。在本研究中，DNA片段化（末端脱氧核苷酸转移酶（TdT）催化的荧光素-12-dUTP DNA末端标记），凋亡细胞死亡的指示，并在细胞增殖的变化进行了检查，在体外37 ℃的控制和热处理（42 ℃，15分钟）GD 10 CD大鼠胚胎。暴露后将胚胎放回37 ℃培养，并在5、8或18小时后进行评价。在CNS、视泡、神经管和体节中观察到与温度相关的TdT标记细胞的增加。用增殖细胞核抗原（PCNA）的细胞特异性丰度和有丝分裂像的定量来检查细胞增殖的变化。在视杯区域的神经外胚层细胞中，PCNA丰度的变化不明显，但观察到有丝分裂像明显减少。两种方法均未检测到体节中细胞增殖的显著变化。这些结果表明，急性高温破坏胚胎发育，通过不适当的细胞死亡和/或改变细胞增殖的发展中的大鼠胚胎的离散区域的组合。此外，出生后的脊椎和肋骨缺陷以下中断体节的发展可能是由于，部分原因是大量的细胞死亡发生在preomitic中胚层。(C)1999 Elsevier Science Inc.
Epidemiologic studies strongly suggest that in utero exposure to hyperthermia results in developmental defects in humans, Rats, mice, guinea pigs, and other species exposed to hyperthermia also exhibit a variety of developmental defects. Studies in our laboratory have focused on exposure to hyperthermia on Gestation Day (GD) 10 of rats in vivo or in vitro. Within 24 h after in vivo or in vitro exposure, delayed or abnormal CNS, optic cup, somite, and limb development can be observed. At birth, only rib and vertebral malformations are seen after hyperthermia on GD 10, and these have been shown to be due to alterations in somite segmentation. Unsegmented somites have been thought to result from a cell-cycle block in the presomitic mesoderm, from which somites emerge individually during normal development. In the present study, DNA fragmentation (terminal deoxynucleotidyl transferase (TdT) catalyzed fluorescein-12-dUTP DNA end-labelling), indicative of apoptotic cell death, and changes in cell proliferation were examined in vitro in 37 degrees C control and heat treated (42 degrees C for 15 min) GD 10 CD rat embryos. Embryos were returned to 37 degrees C culture following exposure and evaluated 5, 8, or 18 h later. A temperature-related increase in TdT labelled cells was observed in the CNS, optic vesicle, neural tube, and somites, Increased cell death in the presomitic mesoderm also was evident. Changes in cell proliferation were examined using the cell-specific abundance of proliferating cell nuclear antigen (PCNA) and the quantification of mitotic figures. In neuroectodermal cells in the region of the optic cup, a change in the abundance of PCNA was not apparent, but a marked decrease in mitotic figures was observed. A significant change in cell proliferation in somites was not detected by either method. These results suggest that acute hyperthermia disrupts embryonic development through a combination of inappropriate cell death and/or altered cell proliferation in discrete regions of the developing rat embryo. Furthermore, postnatal vertebral and rib defects following disrupted somite development may be due, in part, to abundant cell death occurring in the presomitic mesoderm. (C) 1999 Elsevier Science Inc.