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In vitro testicular toxicity models: Opportunities for advancement via biomedical engineering techniques

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Louise Parks Saldutti1, Bruce K. Beyer2, William Breslin3, Terry R. Brown4, Robert E. Chapin5, Sarah Campion5, Brian Enright6, Elaine Faustman7, Paul M. D. Foster8, Thomas Hartung9, William Kelce10, James H. Kim11, Elizabeth G. Loboa12, Aldert H. Piersma13, David Seyler14, Katie J. Turner15, Hanry Yu16, Xiaozhong Yu17, and Jennifer C. Sasaki18
1 Department of Development & Reproduction, Merck & Co., West Point, PA, USA;
2 Department of Disposition, Safety and Animal Research – Preclinical Safety, Sanofi U.S. Inc., Bridgewater, NJ, USA;
3 Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN, USA;
4 Department of Biochemistry & Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;
5 Pfizer Inc., Global R&D, Developmental and Reproductive Toxicology Group, Groton, CT, USA;
6 AbbVie Inc., North Chicago, IL, USA;
7 University of Washington, Department of Environmental and Occupational Health Sciences, Institute for Risk Analysis and Risk Communication, Seattle, WA, USA;
8 National Toxicology Program, National Institutes of Environmental Health Sciences, National Institute of Health, Department of Health and Human Services, Research Triangle Park, NC, USA;
9 Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA, and University of Konstanz, Konstanz, Germany;
10 Leading Edge PharmTox LLC, Durham, NC, USA;
11 ILSI Health and Environmental Sciences Institute, Washington, DC, USA;
12 Loboa: UNC-Chapel Hill and NC State University, Raleigh, NC, USA;
13 Center for Health Protection, RIVM, Bilthoven, The Netherlands and Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands;
14 Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN, USA;
15 Research Triangle Institute, Research Triangle Park, NC, USA;
16 Physiology & Mechanobiology Institute, National University of Singapore; Institute of Bioengineering and Nanotechnology, A*STAR, Singapore; Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;
17 University of Washington, current affiliation Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, USA;
18 AstraZeneca, Global Safety Assessment, Waltham, MA, USA

Summary

To address the pressing need for better in vitro testicular toxicity models, a workshop sponsored by the International Life Sciences Institute (ILSI), the Health and Environmental Science Institute (HESI), and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), was held at the Mt. Washington Conference Center in Baltimore, MD, USA on October 26-27, 2011. At this workshop, experts in testis physiology, toxicology, and tissue engineering discussed approaches for creating improved in vitro environments that would be more conducive to maintaining spermatogenesis and steroidogenesis and could provide more predictive models for testicular toxicity testing. This workshop report is intended to provide scientists with a broad overview of relevant testicular toxicity literature and to suggest opportunities where bioengineering principles and techniques could be used to build improved in vitro testicular models for safety evaluation. Tissue engineering techniques could, conceivably, be immediately implemented to improve existing models. However, it is likely that in vitro testis models that use single or multiple cell types will be needed to address such endpoints as accurate prediction of chemically induced testicular toxicity in humans, elucidation of mechanisms of toxicity, and identification of possible biomarkers of testicular toxicity.

 

Keywords: testicular toxicity, bioengineering, biomedical engineering, in vitro screening

 

 

ALTEX 30(3), 353–377

DOI: 10.14573/altex.2013.3.353


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