Department of Obstetrics and Gynecology,Yangzhou Maternal and Child Health Hospital Yangzhou University Yangzhou, Jiangsu, China.
Animal Core Facility, Nanjing Medical University, Nanjing, China.
Environ Toxicol. 2022 Dec;37(12):2965-2976. doi: 10.1002/tox.23652. Epub 2022 Aug 27.
Perfluorooctanoic acid (PFOA), a member of a group of polyfluorinated and perfluorinated alkyl substances (PFAS), is associated with adverse pregnancy outcomes in mammals. However, the effects of in vivo exposure to PFOA on the female reproductive system and the underlying mechanisms remain unclear. In our study, we constructed a mouse model to investigate whether low-dose PFOA (1 mg/kg/day) or high-dose PFOA (5 mg/kg/day) affect meiosis maturation of oocytes and the potential mechanisms that may be associated with oocyte maturation disorder. Our results indicate that low-dose and high-dose PFOA can lead to impaired oocyte maturation, which is manifested by decreased rate of embryonic foam rupture and first polar body extrusion. Moreover, PFOA exposure harmed the mitochondrial metabolic, resulting in low levels of ATP contents, high reactive oxygen species, aberrant mitochondrial membrane potential. In addition, the proportion of DNA damage marker γ-H2AX was also significantly increased in PFOA exposure oocytes. These changes lead to abnormal arrangements of the spindle and chromosomes during oocyte maturation. In conclusion, our results for the first time illustrated that exposure to PFOA in vivo in female mice impaired the meiosis maturation of oocytes, which provided a basis for studying the mechanism of PFOA reproductive toxicity in female mammals.
全氟辛酸(PFOA),是全氟和多氟烷基物质(PFAS)的成员之一,与哺乳动物的不良妊娠结局有关。然而,体内暴露于 PFOA 对女性生殖系统的影响及其潜在机制仍不清楚。在我们的研究中,我们构建了一个小鼠模型,以研究低剂量(1mg/kg/天)或高剂量(5mg/kg/天)的 PFOA 是否会影响卵母细胞的减数分裂成熟,以及可能与卵母细胞成熟障碍相关的潜在机制。我们的结果表明,低剂量和高剂量的 PFOA 均可导致卵母细胞成熟受损,表现为胚胎泡沫破裂率和第一极体排出率降低。此外,PFOA 暴露还损害了线粒体代谢,导致 ATP 含量降低、活性氧水平升高、线粒体膜电位异常。此外,PFOA 暴露卵母细胞中 DNA 损伤标志物 γ-H2AX 的比例也显著增加。这些变化导致卵母细胞减数分裂成熟过程中纺锤体和染色体的排列异常。总之,我们的研究结果首次表明,体内暴露于 PFOA 会损害雌性小鼠卵母细胞的减数分裂成熟,为研究 PFOA 对雌性哺乳动物生殖毒性的机制提供了依据。