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Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model

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dc.contributor.authorSant, Karilyn E.
dc.contributor.authorJacobs, Haydee M.
dc.contributor.authorXu, Jiali
dc.contributor.authorBorofski, Katrina A.
dc.contributor.authorMoss, Larry G.
dc.contributor.authorMoss, Jennifer B.
dc.contributor.authorTimme-Laragy, Alicia R.
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentDuke University Medical Center
dc.contributor.departmentDuke University Medical Center
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.date2023-09-24T01:36:15.000
dc.date.accessioned2024-04-26T20:12:09Z
dc.date.available2019-12-04T00:00:00Z
dc.date.issued2016-01-01
dc.description.abstractThe pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio). Using endogenously expressed fluorescent protein markers for developing zebrafish beta cells and exocrine pancreas tissue, we documented differences in islet area and incidence rates of islet morphological variants in zebrafish embryos between 48 and 96 h post fertilization (hpf), raised under control conditions commonly used in embryotoxicity assays. We identified critical windows for chemical exposures during which increased incidences of endocrine pancreas abnormalities were observed following exposure to cyclopamine (2–12 hpf), Mono-2-ethylhexyl phthalate (MEHP) (3–48 hpf), and Perfluorooctanesulfonic acid (PFOS) (3–48 hpf). Both islet area and length of the exocrine pancreas were sensitive to oxidative stress from exposure to the oxidant tert-butyl hydroperoxide during a highly proliferative critical window (72 hpf). Finally, pancreatic dysmorphogenesis following developmental exposures is discussed with respect to human disease.
dc.identifier.doihttps://doi.org/10.3390/toxics4030020
dc.identifier.orcidhttps://orcid.org/0000-0001-8565-2072
dc.identifier.urihttps://hdl.handle.net/20.500.14394/42388
dc.relation.ispartofToxics
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1048&context=public_health_faculty_pubs&unstamped=1
dc.rightsUMass Amherst Open Access Policy
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.source.issue3
dc.source.issueZebrafish as a Model for Assessing Chemical Toxicity
dc.source.issue4
dc.source.statuspublished
dc.subjectendocrine pancreas
dc.subjectpancreatic toxicology
dc.subjectbeta cell
dc.subjectzebrafish
dc.subjectexocrine
dc.subjectendocrine disrupting chemicals
dc.subjectmorphology
dc.titleAssessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model
dc.typearticle
dc.typearticle
digcom.contributor.authorisAuthorOfPublication|email:ksant@umass.edu|institution:University of Massachusetts Amherst|Sant, Karilyn E.
digcom.contributor.authorJacobs, Haydee M.
digcom.contributor.authorXu, Jiali
digcom.contributor.authorBorofski, Katrina A.
digcom.contributor.authorMoss, Larry G.
digcom.contributor.authorMoss, Jennifer B.
digcom.contributor.authorTimme-Laragy, Alicia R.
digcom.date.embargo2019-12-04T00:00:00-08:00
digcom.identifierpublic_health_faculty_pubs/49
digcom.identifier.contextkey15921333
digcom.identifier.submissionpathpublic_health_faculty_pubs/49
dspace.entity.typePublication
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