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发育过程中接触内分泌干扰物滴滴涕会干扰胸腺的衰老性萎缩。

Developmental Exposure to Endocrine Disrupter DDT Interferes with Age-Related Involution of Thymus.

机构信息

Laboratory of Endocrine System Development, Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 119991 Moscow, Russia.

Department of Histology, Cytology, and Embryology, Federal State Funded Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia.

出版信息

Int J Mol Sci. 2022 Jun 15;23(12):6678. doi: 10.3390/ijms23126678.

Abstract

The impact of endocrine-disrupting chemicals on the development and involution of the immune system is a possible reason for the increased incidence of disorders associated with inappropriate immune function. The thymus is a lymphoid and also an endocrine organ, and, accordingly, its development and functioning may be impaired by endocrine disruptors. The aim was to evaluate age-related thymus involution in mature rats exposed to the endocrine disruptor DDT during prenatal and postnatal ontogeny. Methodology included in vivo experiment on male Wistar rats exposed to low doses of DDT during prenatal and postnatal development and morphological assessment of thymic involution, including the immunohistochemical detection of proliferating thymocytes. The study was carried out at the early stage of involution. Results: DDT-exposed rats exhibited a normal anatomy, and the relative weight of the thymus was within the control ranges. Histological and immunohistochemical examinations revealed increased cellularity of the cortex and the medulla, higher content of lymphoblasts, and more intensive proliferation rate of thymocytes compared to the control. Evaluation of thymic epithelial cells revealed a higher rate of thymic corpuscles formation. Conclusion: The data obtained indicate that endocrine disrupter DDT disturbs postnatal development of the thymus. Low-dose exposure to DDT during ontogeny does not suppress growth rate but violates the developmental program of the thymus by slowing down the onset of age-related involution and maintaining high cell proliferation rate. It may result in excessive formation of thymus-dependent areas in peripheral lymphoid organs and altered immune response.

摘要

内分泌干扰化学物质对免疫系统的发育和退化的影响是导致与免疫功能不当相关的疾病发病率增加的一个可能原因。胸腺是淋巴器官,也是内分泌器官,因此其发育和功能可能会受到内分泌干扰物的损害。目的是评估暴露于内分泌干扰物滴滴涕的成熟大鼠的胸腺退化与年龄的相关性,该研究涉及在产前和产后发育过程中对雄性 Wistar 大鼠进行滴滴涕的体内实验,以及对胸腺退化的形态评估,包括增殖性胸腺细胞的免疫组织化学检测。该研究在退化的早期阶段进行。结果:暴露于滴滴涕的大鼠表现出正常的解剖结构,胸腺的相对重量在对照组的范围内。组织学和免疫组织化学检查显示,皮质和髓质的细胞增多,淋巴母细胞含量较高,与对照组相比,胸腺细胞的增殖率更高。对胸腺上皮细胞的评估表明,胸腺小体的形成率更高。结论:获得的数据表明,内分泌干扰物滴滴涕扰乱了胸腺的产后发育。在个体发育过程中低剂量接触滴滴涕不会抑制生长速度,而是通过减缓与年龄相关的退化的发生并维持高细胞增殖率来破坏胸腺的发育程序。这可能导致外周淋巴器官中过度形成依赖于胸腺的区域,并改变免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/024b/9223823/dc6f4fe2804b/ijms-23-06678-g001.jpg

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