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阐明雌性斑马鱼的生殖毒性机制:一生暴露于三(2-氯乙基)磷酸酯的转录组学研究。

Elucidating the reproductive toxicity mechanisms in female zebrafish: A transcriptomic study of lifetime tris(2-chloroethyl) phosphate exposure.

机构信息

State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Technology Innovation Center for Monitoring and Restoration Engineering of Ecological Fragile Zone in Southeast China, Ministry of Natural Resources, Fuzhou 350001, China.

State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

出版信息

Sci Total Environ. 2024 Oct 20;948:174831. doi: 10.1016/j.scitotenv.2024.174831. Epub 2024 Jul 15.

DOI:10.1016/j.scitotenv.2024.174831
PMID:39019278
Abstract

Tris(2-chloroethyl) phosphate (TCEP), emerging as a predominant substitute for brominated flame retardants (BFRs), is now increasingly recognized as a prevalent contaminant in aquatic ecosystems. The extent of its reproductive toxicity in aquatic species, particularly in zebrafish (Danio rerio), remains insufficiently characterized. This study subjected zebrafish embryos to various concentrations of TCEP (0, 0.8, 4, 20, and 100 μg/L) over a period of 120 days, extending through sexual maturation, to assess its impact on female reproductive health. Notable reductions in body weight (0.59- and 0.76-fold) and length (0.71- and 0.77-fold) were observed at concentrations of 20 and 100 μg/L, with a concomitant decrease by 0.21- to 0.61-fold in the gonadal somatic index across all treatment groups. The reproductive output, as evidenced by egg production and hatchability, was adversely affected. Histopathological analysis suggested that TCEP exposure impedes ovarian development. Endocrine alterations were also evident, with testosterone and 11-ketotestosterone levels significantly diminished by 0.38- and 0.08-fold at the highest concentration tested, while 17β-estradiol was elevated by 0.09- to 0.14-fold in all exposed groups. Transcriptomic profiling illuminated numerous differentially expressed genes (DEGs) integral to reproductive processes, including hormone regulation, neuroactive ligand-receptor interactions, oocyte meiosis, and progesterone-mediated maturation pathways. Collectively, these findings indicate that lifelong exposure to TCEP disrupts ovarian development and maturation in female zebrafish, alters gene expression within the hypothalamic-pituitary-gonadal axis, and perturbs sex hormone synthesis, culminating in pronounced reproductive toxicity.

摘要

三(2-氯乙基)磷酸酯(TCEP)作为溴化阻燃剂(BFRs)的主要替代品,现已被广泛认为是水生生态系统中的一种普遍污染物。其对水生物种,特别是斑马鱼(Danio rerio)的生殖毒性程度尚未得到充分描述。本研究将斑马鱼胚胎暴露于不同浓度的 TCEP(0、0.8、4、20 和 100μg/L)中 120 天,直至性成熟,以评估其对雌性生殖健康的影响。在 20 和 100μg/L 浓度下,观察到体重(降低 0.59-和 0.76 倍)和长度(降低 0.71-和 0.77 倍)显著降低,所有处理组的性腺体指数均降低 0.21-0.61 倍。生殖产出,如产卵量和孵化率,受到不利影响。组织病理学分析表明 TCEP 暴露会阻碍卵巢发育。内分泌变化也很明显,最高测试浓度下,睾酮和 11-酮睾酮水平分别降低 0.38-和 0.08 倍,而所有暴露组的 17β-雌二醇水平升高 0.09-0.14 倍。转录组谱分析揭示了许多与生殖过程相关的差异表达基因(DEGs),包括激素调节、神经活性配体-受体相互作用、卵母细胞减数分裂和孕酮介导的成熟途径。总的来说,这些发现表明终生暴露于 TCEP 会破坏雌性斑马鱼的卵巢发育和成熟,改变下丘脑-垂体-性腺轴内的基因表达,并扰乱性激素合成,导致明显的生殖毒性。

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