Perfluorononanoic acid impedes mouse oocyte maturation by inducing mitochondrial dysfunction and oxidative stress.
Perfluorononanoic acid impedes mouse oocyte maturation by inducing mitochondrial dysfunction and oxidative stress.
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全氟农酸通过诱导线粒体功能障碍和氧化应激来阻碍小鼠卵母细胞成熟。
DOI：
10.1016/j.reprotox.2021.07.002
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Qiao H
中科院分区：
文献类型：
--
作者：
Jiao X;Liu N;Xu Y;Qiao H
全氟农酸(PFNA)是PFAS的成员之一，在人体血液和组织中经常检测到，甚至在女性卵泡液中也有检测到。接触全氟辛烷磺酸，而不是全氟辛烷磺酸和全氟辛烷磺酸，与流产和延长怀孕时间呈正相关。毒理学研究表明，接触PFNA与动物的免疫毒性、肝脏毒性、发育毒性和生殖毒性有关。然而，关于PFNA对卵母细胞成熟的毒性影响的信息很少。在本研究中，我们研究了PFNA暴露对小鼠卵母细胞体外成熟的毒性效应。结果表明，600μ-M-PFNA能显著抑制小鼠卵母细胞生发泡破裂和极体排出。我们的进一步研究表明，PFNA诱导了异常的中期I(MI)纺锤体组装，证明了纺锤体的畸形和p-ERK1/2在PFNA处理的卵母细胞中的错误定位。我们还发现，PFNA导致线粒体分布异常，线粒体膜电位增加。因此，PFNA增加了活性氧物种(ROS)的水平，导致氧化应激，DNA损伤，并最终导致卵母细胞早期凋亡。此外，培养14h后，PFNA可破坏大多数极体卵母细胞中期II(MII)纺锤体的形成。总之，我们的结果表明，PFNA通过破坏纺锤体组装、破坏线粒体功能、诱导氧化应激、DNA损伤和早期细胞凋亡来干扰卵母细胞的体外成熟。
Perfluorononanoic acid (PFNA), a member of PFAS, is frequently detected in human blood and tissues, even in follicular fluid of women. The exposure of PFNA, but not PFOA and PFOS, is positively correlated with miscarriage and increased time to pregnancy. Toxicological studies indicated that PFNA exposure is associated with immunotoxicity, hepatotoxicity, developmental toxicity, and reproductive toxicity in animals. However, there is little information regarding the toxic effects of PFNA on oocyte maturation. In this study, we investigated the toxic effects of PFNA exposure on mouse oocyte maturation in vitro. Our results showed that 600 μM PFNA significantly inhibited germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Our further study revealed that PFNA induced abnormal metaphase I (MI) spindle assembly, evidenced by malformed spindles and mislocalization of p-ERK1/2 in PFNA-treated oocytes. We also found that PFNA induced abnormal mitochondrial distribution and increased mitochondrial membrane potential. Consequently, PFNA increased reactive oxygen species (ROS) levels, leading to oxidative stress, DNA damage, and eventually early-stage apoptosis in oocytes. In addition, after 14 h culture, PFNA disrupted the formation of metaphase II (MII) spindle in most PFNA-treated oocytes with polar bodies. Collectively, our results indicate that PFNA interferes with oocyte maturation in vitro via disrupting spindle assembly, damaging mitochondrial functions, and inducing oxidative stress, DNA damage, and early-stage apoptosis.
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影响因子：
10.4
作者：
Calafat, Antonia M;Wong, Lee-Yang;Kuklenyik, Zsuzsanna;Reidy, John A;Needham, Larry L
通讯作者：
Needham, Larry L
影响因子：
3.3
作者：
Das, Kaberi P.;Grey, Brian E.;Lau, Christopher
通讯作者：
Lau, Christopher
影响因子：
4
作者：
Kilani, Suha;Cooke, Simon;Chapman, Michael
通讯作者：
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影响因子：
13.6
作者：
Heo, Jin-Ju;Lee, Ji-Woo;Oh, Jeong-Eun
通讯作者：
Oh, Jeong-Eun
影响因子：
3.8
作者：
Ding, Zhi-Ming;Zhang, Shou-Xin;Huo, Li-Jun
通讯作者：
Huo, Li-Jun