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青春期接触三(1,3-二氯-2-丙基)磷酸酯(TCPP)通过破坏下丘脑-垂体-性腺轴导致斑马鱼生殖毒性。

Adolescent exposure to tris(1,3-dichloro-2-propyl) phosphate (TCPP) induces reproductive toxicity in zebrafish through hypothalamic-pituitary-gonadal axis disruption.

机构信息

School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.

Key Laboratory of Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.

出版信息

Sci Total Environ. 2024 Nov 25;953:176096. doi: 10.1016/j.scitotenv.2024.176096. Epub 2024 Sep 10.

DOI:10.1016/j.scitotenv.2024.176096
PMID:39260506
Abstract

Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.

摘要

三(1,3-二氯-2-丙基)磷酸酯(TCPP)是一种普遍存在于水生环境中的有机磷阻燃剂,其生态风险引起了广泛关注。本研究旨在探讨 TCPP 对斑马鱼生殖功能的影响,并阐明其性别相关的毒性机制。通过评估 10mg/L TCPP 从受精后 30 至 120 天(dpf)暴露对斑马鱼的影响,我们全面评估了其生殖能力和内分泌系统的改变。研究结果表明,TCPP 暴露破坏了斑马鱼的性别分化,显著损害了其生殖能力,导致产卵量减少和后代发育质量下降。对性腺组织的组织学分析显示,雌性幼稚卵母细胞异常增加,雄性成熟精子计数和精原细胞结构完整性降低,共同导致胚胎质量受损。此外,分子对接结果表明,TCPP 与雌激素受体具有很强的亲和力,TCPP 处理的斑马鱼表现出性激素失衡和雌激素受体表达增加。与下丘脑-垂体-性腺(HPG)轴相关的基因改变和类固醇生成途径的激活表明,TCPP 靶向 HPG 轴以调节性激素稳态。他莫昔芬(TAM)作为雌激素的竞争性抑制剂,表现出双相作用,在 TAM 加入后,TCPP 诱导的效应在雄性和雌性斑马鱼中均得到了拮抗。总的来说,本研究强调了 TCPP 暴露对斑马鱼生殖功能的性别依赖性毒性,表现为生殖能力下降和激素紊乱,这可能是由于 HPG 轴和类固醇生成途径受到干扰所致。这些发现强调了在进行生态系统化学风险评估时考虑性别差异的重要性,并突出了理解化学污染物对水生物种生殖健康影响的机制的重要性。

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