Division of Reproduction, Department of Clinical Sciences & the Centre for Reproductive biology in Uppsala, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Department of Information Technology, and SciLifeLab BioImage Informatics Facility, Uppsala University, Uppsala, Sweden.
PLoS One. 2022 Dec 28;17(12):e0279551. doi: 10.1371/journal.pone.0279551. eCollection 2022.
The objectives of this study were to evaluate the effect of perfluoroalkyl substances on early embryonic development and apoptosis in blastocysts using a porcine in vitro model. Porcine oocytes (N = 855) collected from abattoir ovaries were subjected to perfluorooctane sulfonic acid (PFOS) (0.1 μg/ml) and perfluorohexane sulfonic acid (PFHxS) (40 μg/ml) during in vitro maturation (IVM) for 45 h. The gametes were then fertilized and cultured in vitro, and developmental parameters were recorded. After 6 days of culture, resulting blastocysts (N = 146) were stained using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and imaged as stacks using confocal laser scanning microscopy. Proportion of apoptotic cells as well as total numbers of nuclei in each blastocyst were analyzed using objective image analysis. The experiment was run in 9 replicates, always with a control present. Effects on developmental parameters were analyzed using logistic regression, and effects on apoptosis and total numbers of nuclei were analyzed using linear regression. Higher cell count was associated with lower proportion of apoptotic cells, i.e., larger blastocysts contained less apoptotic cells. Upon PFAS exposure during IVM, PFHxS tended to result in higher blastocyst rates on day 5 post fertilization (p = 0.07) and on day 6 post fertilization (p = 0.05) as well as in higher apoptosis rates in blastocysts (p = 0.06). PFHxS resulted in higher total cell counts in blastocysts (p = 0.002). No effects attributable to the concentration of PFOS used here was seen. These findings add to the evidence that some perfluoroalkyl substances may affect female reproduction. More studies are needed to better understand potential implications for continued development as well as for human health.
本研究旨在通过猪体外模型评估全氟烷基物质(PFAS)对早期胚胎发育和囊胚细胞凋亡的影响。从屠宰场卵巢中采集的猪卵母细胞(N=855)在体外成熟(IVM)期间接受全氟辛烷磺酸(PFOS)(0.1μg/ml)和全氟己烷磺酸(PFHxS)(40μg/ml)处理,共 45 小时。然后,将配子受精并在体外培养,并记录发育参数。培养 6 天后,用末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)法对囊胚进行染色,并使用共聚焦激光扫描显微镜对其进行堆叠成像。使用客观图像分析分析每个囊胚中凋亡细胞的比例和总核数。该实验进行了 9 次重复,每次均有对照。使用逻辑回归分析发育参数的影响,使用线性回归分析凋亡和总核数的影响。较高的细胞计数与较低的凋亡细胞比例相关,即较大的囊胚包含较少的凋亡细胞。在 IVM 期间暴露于 PFAS 时,PFHxS 倾向于在受精后第 5 天(p=0.07)和第 6 天(p=0.05)导致更高的囊胚率,以及在囊胚中导致更高的凋亡率(p=0.06)。PFHxS 导致囊胚中的总细胞计数增加(p=0.002)。未观察到与所用 PFOS 浓度相关的影响。这些发现增加了一些全氟烷基物质可能影响女性生殖的证据。需要更多的研究来更好地了解对持续发育以及对人类健康的潜在影响。