TY - JOUR
T1 - High-content analysis provides mechanistic insights into the testicular toxicity of Bisphenol A and selected analogues in mouse spermatogonial cells
AU - Liang, Shenxuan
AU - Yin, Lei
AU - Yu, Kevin Shengyang
AU - Hofmann, Marie Claude
AU - Yu, Xiaozhong
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
PY - 2017/1
Y1 - 2017/1
N2 - Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose- and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction.
AB - Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose- and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction.
KW - And tetrabromobisphenol A
KW - Bisphenol A
KW - Bisphenol AF
KW - Bisphenol S
KW - C18-4 spermatogonial cell line
KW - Cell cycle
KW - Cytoskeleton
KW - DNA damage responses
KW - High-content analysis
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U2 - 10.1093/toxsci/kfw178
DO - 10.1093/toxsci/kfw178
M3 - Article
C2 - 27633978
AN - SCOPUS:85014346991
SN - 1096-6080
VL - 155
SP - 43
EP - 60
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -