暴露于邻苯二甲酸丁苄酯(BBP)会导致秀丽隐杆线虫双链断裂形成增加和生殖系功能障碍。

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2024-10-24 eCollection Date: 2024-10-01 DOI:10.1371/journal.pgen.1011434
Ayana L Henderson, Rajendiran Karthikraj, Emma L Berdan, Shannan Ho Sui, Kurunthachalam Kannan, Monica P Colaiácovo
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引用次数: 0

摘要

邻苯二甲酸丁苄酯(BBP)是一种增塑剂,广泛存在于乙烯基地板、地毯衬垫、食品包装、个人护理产品和儿童玩具等消费品中。尽管有证据表明,接触 BBP 会扰乱雄性和雌性配子的完整性,但对其对早期减数分裂事件的直接影响却研究不足。在这里,我们利用线虫秀丽隐杆线虫(Caenorhabditis elegans),利用高通量筛选平台测量了 BBP 暴露对 X 染色体非异型连接率的影响,结果表明 BBP 暴露对 X 染色体非异型连接率的影响是非单调剂量反应。在测试的剂量范围(1、10、100 和 500 μM BBP)中,我们发现 10 μM BBP 对生殖细胞的影响最大,导致生殖细胞凋亡增加和染色体组织缺陷。质谱分析表明,秀丽隐杆线虫能有效地将 BBP 代谢为其主要代谢产物--邻苯二甲酸单丁酯(MBP)和邻苯二甲酸单苄酯(MBzP),而且在蠕虫体内检测到的 BBP、MBP 和 MBzP 含量与在人类生物样本中检测到的含量相符。暴露于 10 μM BBP 会导致生殖细胞有丝分裂核增大、减数分裂进程改变、p53/CEP-1 依赖性 DNA 损伤检查点激活、整个生殖细胞的双链断裂水平增加、卵母细胞在二分裂期染色体形态缺陷以及氧化应激增加。RNA 测序分析表明,暴露于 BBP 会导致参与异生物代谢过程、细胞外基质组织、卵母细胞形态发生、减数分裂细胞周期和氧化还原的基因表达发生改变。综上所述,我们认为暴露于 BBP 会导致氧化应激增加和双链断裂的形成,从而损害种系基因组的完整性和染色体的分离。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exposure to benzyl butyl phthalate (BBP) leads to increased double-strand break formation and germline dysfunction in Caenorhabditis elegans.

Benzyl butyl phthalate (BBP), a plasticizer found in a wide range of consumer products including vinyl flooring, carpet backing, food packaging, personal care products, and children's toys, is an endocrine-disrupting chemical linked to impaired reproduction and development in humans. Despite evidence that BBP exposure perturbs the integrity of male and female gametes, its direct effect on early meiotic events is understudied. Here, using the nematode Caenorhabditis elegans, we show that BBP exposure elicits a non-monotonic dose response on the rate of X-chromosome nondisjunction measured using a high-throughput screening platform. From among the range of doses tested (1, 10, 100 and 500 μM BBP), we found that 10 μM BBP elicited the strongest effect on the germline, resulting in increased germ cell apoptosis and chromosome organization defects. Mass spectrometry analysis shows that C. elegans efficiently metabolizes BBP into its primary metabolites, monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP), and that the levels of BBP, MBP, and MBzP detected in the worm are within the range detected in human biological samples. Exposure to 10 μM BBP leads to germlines with enlarged mitotic nuclei, altered meiotic progression, activation of a p53/CEP-1-dependent DNA damage checkpoint, increased double-strand break levels throughout the germline, chromosome morphology defects in oocytes at diakinesis, and increased oxidative stress. RNA sequencing analysis indicates that BBP exposure results in the altered expression of genes involved in xenobiotic metabolic processes, extracellular matrix organization, oocyte morphogenesis, meiotic cell cycle, and oxidoreduction. Taken together, we propose that C. elegans exposure to BBP leads to increased oxidative stress and double-strand break formation, thereby compromising germline genomic integrity and chromosome segregation.

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来源期刊
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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