Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group.
Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group.
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DOI：
10.1111/cpr.13353
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发表时间：
2023-02
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
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全氟烷基和多氟烷基物质（PFAS）是广泛用于各种产品的人造化学品。PFAS的特征在于它们的氟化碳链，这使得它们难以在人和动物中降解和生物累积。毒理学研究表明PFAS具有毒性作用：细胞毒性、免疫毒性、神经毒性和生殖毒性。然而，目前尚不清楚PFAS的结构（如碳链长度和官能团）如何决定其生殖毒性。通过使用小鼠卵母细胞体外成熟（IVM）系统，我们发现两种主要类别的PFAS，全氟烷基羧酸（PFCA）和全氟烷基磺酸（PFSA）的毒性随着碳链长度的增加和磺酸酯基团的加入而升高。具体而言，在600 μM时，全氟己磺酸（PFHxS）和全氟辛烷磺酸（PFOS）降低了胚芽囊泡破裂（GVBD）和极体挤出（PBE）的速率以及增大的极体。然而，较短的PFSA，全氟丁磺酸（PFBS），和所有PFCA没有表现出类似的不良细胞毒性。此外，我们发现600 μM PFHxS和PFOS暴露诱导过量的活性氧（ROS）和线粒体膜电位（MMP）降低。细胞骨架分析表明，PFHxS和PFOS暴露诱导染色体错位，异常F-肌动蛋白组织，细长纺锤体形成，并在处理的卵母细胞对称分裂。这些减数分裂缺陷损害了孤雌激活后卵母细胞的发育能力。我们的研究为PFAS的结构-毒性关系提供了新的信息。PFAS的生殖毒性取决于其化学结构。PFAS的毒性效应与碳链长度之间呈倒U形关系;碳链长度约为10时毒性最大。与PFCA相比，PFSA对小鼠卵母细胞成熟的毒性作用更高且独特，因为PFSA具有额外的磺酸基团。
Per‐ and polyfluoroalkyl substances (PFAS) are man‐made chemicals that are widely used in various products. PFAS are characterized by their fluorinated carbon chains that make them hard to degrade and bioaccumulate in human and animals. Toxicological studies have shown PFAS toxic effects: cytotoxicity, immunotoxicity, neurotoxicity, and reproductive toxicity. However, it is still unclear how the structures of PFAS, such as carbon‐chain length and functional groups, determine their reproductive toxicity. By using a mouse‐oocyte‐in‐vitro‐maturation (IVM) system, we found the toxicity of two major categories of PFAS, perfluoroalkyl carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA), is elevated with increasing carbon‐chain length and the inclusion of the sulfonate group. Specifically, at 600 μM, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) reduced the rates of both germinal‐vesicle breakdown (GVBD) and polar‐body extrusion (PBE) as well as enlarged polar bodies. However, the shorter PFSA, perfluorobutanesulfonic acid (PFBS), and all PFCA did not show similar adverse cytotoxicity. Further, we found that 600 μM PFHxS and PFOS exposure induced excess reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Cytoskeleton analysis revealed that PFHxS and PFOS exposure induced chromosome misalignment, abnormal F‐actin organization, elongated spindle formation, and symmetric division in the treated oocytes. These meiotic defects compromised oocyte developmental competence after parthenogenetic activation. Our study provides new information on the structure‐toxicity relationship of PFAS. Reproductive toxicity of PFAS is determined by their chemical structures. An inverted U‐shaped relationship is shown between toxic effects of PFAS and carbon‐chain length; carbon‐chain length around 10 is the most toxic. PFSA has higher and unique toxicity effects on mouse oocyte maturation compared to PFCA because PFSA has an extra sulfonate group.
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DOI：
10.1073/pnas.93.14.7032
发表时间：
1996-07-09
影响因子：
11.1
作者：
Choi, TS;Fukasawa, K;VandeWoude, GF
通讯作者：
VandeWoude, GF
影响因子：
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影响因子：
9.2
作者：
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Verlhac, Marie-Helene
DOI：
10.1007/978-1-60761-376-3_4
发表时间：
2009-01-01
期刊：
CYTOSKELETON METHODS AND PROTOCOLS
影响因子：
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作者：
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通讯作者：
Holzinger, Andreas
DOI：
10.1039/d0em00355g
发表时间：
2020-12-16
期刊：
Environmental science. Processes & impacts
影响因子：
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作者：
Cousins IT;DeWitt JC;Glüge J;Goldenman G;Herzke D;Lohmann R;Ng CA;Scheringer M;Wang Z
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Wang Z