TY - JOUR
T1 - Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group
AU - Feng, Jianan
AU - Soto-Moreno, Edgar J.
AU - Prakash, Aashna
AU - Balboula, Ahmed Z.
AU - Qiao, Huanyu
N1 - Funding Information:
We would like to thank Dr. Joseph Irudayaraj for kindly sharing all PFAS chemicals used in this study. We also thank Drs. Michael Spinella, Sarah Freemantle, Jodi Flaws, and Wenyan Mei for their technical support and Dr. Jodi Flaws for her comments on this manuscript. This work was supported by National Institutions of Health (NIH) R00HD082375, R01GM135549 and R35GM142537.
Publisher Copyright:
© 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
PY - 2023/2
Y1 - 2023/2
N2 - Objectives: 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. Methods and Results: 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. Conclusions: Our study provides new information on the structure-toxicity relationship of PFAS.
AB - Objectives: 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. Methods and Results: 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. Conclusions: Our study provides new information on the structure-toxicity relationship of PFAS.
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U2 - 10.1111/cpr.13353
DO - 10.1111/cpr.13353
M3 - Article
C2 - 36305033
AN - SCOPUS:85141407918
SN - 0960-7722
VL - 56
JO - Cell Proliferation
JF - Cell Proliferation
IS - 2
M1 - e13353
ER -