High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

Details

• Personal Author:
  Hofmann M-C ; Liang S ; Shengyang Yu K ; Yin L ; Yu X
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Endocrine System Laboratories Occupational Health Safety Toxicology Urogenital System
• Keywords:
  Author Keywords: C18-4 Spermatogonial Cell Line Bisphenol A Bisphenol AF Bisphenol S Cell Cycle Cytoskeleton. Deoxyribonucleic Acids DNA DNA Damage Responses Endocrine Disruptors High-content Analysis Laboratory Animals Reproductive System Tetrabromobisphenol A

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; Maryland ; OSHA Region 3 ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  43-60
• Volume:
  155
• Issue:
  1
• NIOSHTIC Number:
  nn:20051288
• Citation:
  Toxicol Sci 2017 Jan; 155(1):43-60
• Contact Point Address:
  Xiaozhong Yu, Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602
• Email:
  yuxz@uga.edu
• Federal Fiscal Year:
  2017
• Performing Organization:
  University of Georgia, Athens
• Peer Reviewed:
  True
• Start Date:
  20130901
• Source Full Name:
  Toxicological Sciences
• End Date:
  20160831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:08354ab1f94681f0e46007206d92f7a82c825dfde9e3c9908ef7f5d920f9a11b06d9c56f08a26463c4df991677df2d7cd4d56577a54817f97c7b295f02a06beb
• Download URL:
  https://stacks.cdc.gov/view/cdc/211334/cdc_211334_DS1.pdf
• File Type:
  [PDF - 2.30 MB ]