title: Uncovering system-specific stress signatures in primate teeth with multimodal imaging.
abstract: Early life stress can disrupt development and negatively impact long-term health trajectories. Reconstructing histories of early life exposure to external stressors is hampered by the absence of retrospective time-specific biomarkers. Defects in tooth enamel have been used to reconstruct stress but the methods used are subjective and do not identify the specific biological systems impacted by external stressors. Here we show that external physical and social stressors impart biochemical signatures in primate teeth that can be retrieved to objectively reconstruct the timing of early life developmental disruptions. Using teeth from captive macaques, we uncovered elemental imprints specific to disruptions of skeletal growth, including major disruptions in body weight trajectory and moderate to severe illnesses. Discrete increases in heat shock protein-70 expression in dentine coincided with elemental signatures, confirming that elemental signals were associated with activation of stress-related pathways. To overcome limitations of conventional light-microscopic analysis, we used high resolution Raman microspectral imaging to identify structural and compositional alterations in enamel and dentine that coincided with elemental signatures and with detailed medical and behavioural data. Integrating these objective biochemical markers with temporal mapping of teeth enables the retrospective study of early life developmental disruptions and their ensuing health sequelae.
authors.affiliation: Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Faculty of Dentistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Austin
authors.affiliation: Department of Human Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Smith
authors.affiliation: Faculty of Dentistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Ramin M Z
authors.initials: RM
authors.lastname: Farahani
authors.affiliation: Department of Human Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|School of Human Evolution and Social Change, Center for Evolution and Medicine, Arizona State University, Arizona, 85287, USA.|California National Primate Research Center, Davis, California 95616, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Hinde
authors.affiliation: Vibrational Spectroscopy Core Facility, The University of Sydney, Sydney, New South Wales 2006, Australia.|School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Carter
authors.affiliation: Vibrational Spectroscopy Core Facility, The University of Sydney, Sydney, New South Wales 2006, Australia.|School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Joonsup
authors.initials: J
authors.lastname: Lee
authors.affiliation: Vibrational Spectroscopy Core Facility, The University of Sydney, Sydney, New South Wales 2006, Australia.|School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lay
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Kennedy
authors.affiliation: Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Babak
authors.initials: B
authors.lastname: Sarrafpour
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Wright
authors.affiliation: Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.affiliation: Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Faculty of Dentistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Manish
authors.initials: M
authors.lastname: Arora
mesh_terms: D000818:Animals; D015415:Biomarkers; D003804:Dentin / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D064847:Multimodal Imaging; D011323:Primates; D012189:Retrospective Studies; D013059:Spectrum Analysis, Raman; D013312:Stress, Physiological; D013315:Stress, Psychological; D014070:Tooth / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins