Kim Ki Hyung, Kim Juil, Han Jae Yong, Moon Yuseok
1Department of Biomedical Sciences, Biomedical Research Institute, Pusan National University, Yangsan, 50612 Republic of Korea.
2Biomedical Research Institute and Pusan Cancer Center, Busan National University Hospital, Busan, Republic of Korea.
Mol Cell Toxicol. 2019;15(4):443-452. doi: 10.1007/s13273-019-0048-2. Epub 2019 Sep 30.
Heavy metals affect various processes in the embryonic development. Embryonic fibroblasts (EFs) play key roles in the innate recognition and wound healing in reproductive tissues.
Based on the relative toxicities of different inorganic metals and inorganic nonmetallic compounds against murine and chicken EF cells, mechanistic estimations were performed based on transcriptomic analyses.
Lead (II) acetate induced preferential injuries in the chicken EF and mechanistic analyses using transcriptome revealed that chemokine receptor-associated events are potently involved in metal-induced adverse actions. As an early sentinel of metal exposure, the precision-cut intestine slices (PCIS) induced the expression of chemokines including CXCLi1 or CXCLi2, which were potent gut-derived factors that activate chemokine receptors in reproductive organs after circulation.
EF-selective metals can be estimated to trigger the chemokine circuit in the gut-reproductive axis of chickens. This methodology using PCIS-EF culture could be used as a promising alternate platform for the reproductive immunotoxicological assessment.
重金属会影响胚胎发育的各个过程。胚胎成纤维细胞(EFs)在生殖组织的先天识别和伤口愈合中起关键作用。
基于不同无机金属和无机非金属化合物对小鼠和鸡EF细胞的相对毒性,进行基于转录组分析的机制评估。
醋酸铅(II)对鸡EF造成优先损伤,利用转录组进行的机制分析表明趋化因子受体相关事件有力地参与了金属诱导的不良反应。作为金属暴露的早期哨兵,精密切割肠片(PCIS)诱导趋化因子表达,包括CXCLi1或CXCLi2,这些是有效的肠道衍生因子,在循环后激活生殖器官中的趋化因子受体。
可估计EF选择性金属会触发鸡肠道-生殖轴中的趋化因子回路。这种使用PCIS-EF培养的方法可作为生殖免疫毒理学评估的一个有前景的替代平台。