Hyperthermia: malformations to chaperones

Bennett, Gregg

doi:10.1002/bdrb.20254

Cited by 31 publications

(19 citation statements)

References 130 publications

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“…Some studies report that exposures to high temperature may cause cell death in fetuses, subsequently resulting in congenital anomalies (Bennett 2010). Cellular death may also occur if elevated temperatures cause placental insufficiency or trigger a heat-shock response.…”

Section: Discussionmentioning

confidence: 99%

“…While the heat-shock response typically is short lived, interruption of normal biochemical and molecular events during crucial periods of development could have implications for the fetus. In rat models, the duration of the heat-shock response is correlated with risk of heart defects due to heat (Bennett 2010). Elevated ambient temperatures are unlikely to cause a severe heat-shock response in pregnant women, but heat waves have the potential to trigger mild responses with a plausible impact on noncritical or atrial septal defects, especially beginning the 3rd week postconception.…”

Section: Discussionmentioning

confidence: 99%

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Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy

Auger

Fraser

Sauvé

et al. 2017

Environ Health Perspect

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Background:Congenital heart defects may be environmentally related, but the association with elevated ambient temperature has received little attention.Objectives:We studied the relationship between outdoor heat during the first trimester of pregnancy and risk of congenital heart defects.Methods:We carried out a retrospective cohort study of 704,209 fetuses between 2 and 8 weeks postconception from April to September in Quebec, Canada, 1988–2012. We calculated the prevalence of congenital heart defects at birth according to the number of days women were exposed to maximum temperature ≥ 30°C. In log-binomial regression models, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the relationship of temperature with seven critical and eight noncritical heart defects, adjusted for pregnancy characteristics.Results:Prevalence of congenital heart defects was 979.5 per 100,000 for 10 days or more of temperature ≥ 30°C compared with 878.9 per 100,000 for 0 days of exposure. Temperature was more precisely associated with noncritical than critical defects, which had lower prevalence. Fetuses exposed to 15 days of temperature ≥ 30°C between 2 and 8 weeks postconception had 1.06 times the risk of critical defects (95% CI: 0.67, 1.67) and 1.12 times the risk of noncritical defects (95% CI: 0.98, 1.29) relative to 0 days. Associations were higher for atrial septal defects (PR 1.37, 95% CI: 1.10, 1.70) than for other noncritical defects. For atrial septal defects, associations with elevated temperatures began the 3rd week postconception.Conclusions:Extreme heat exposure during the first trimester may be associated with noncritical heart defects, especially of the atrial septum.Citation:Auger N, Fraser WD, Sauve R, Bilodeau-Bertrand M, Kosatsky T. 2017. Risk of congenital heart defects after ambient heat exposure early in pregnancy. Environ Health Perspect 125:8–14; http://dx.doi.org/10.1289/EHP171

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy

Auger

Fraser

Sauvé

et al. 2017

Environ Health Perspect

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“…2 ° C) result in the recruitment of heat shock proteins which provide protection for proteins against damage by teratogenic doses of heat ( 1 2 ° C). This is accomplished through the attachment to uncovered active sites, thus preventing their binding with other functionally impaired aggregate proteins [Bennett, 2010]. The exact mechanism responsible for altered somitogenesis associated with heat is uncertain.…”

Section: Parental Risk Factors Associated With Cvmmentioning

confidence: 99%

Clinical, Genetic and Environmental Factors Associated with Congenital Vertebral Malformations

Giampietro

Raggio

Blank³

et al. 2012

Mol Syndromol

105

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Congenital vertebral malformations (CVM) pose a significant health problem because they can be associated with spinal deformities, such as congenital scoliosis and kyphosis, in addition to various syndromes and other congenital malformations. Additional information remains to be learned regarding the natural history of congenital scoliosis and related health problems. Although significant progress has been made in understanding the process of somite formation, which gives rise to vertebral bodies, there is a wide gap in our understanding of how genetic factors contribute to CVM development. Maternal diabetes during pregnancy most commonly contributes to the occurrence of CVM, followed by other factors such as hypoxia and anticonvulsant medications. This review highlights several emerging clinical issues related to CVM, including pulmonary and orthopedic outcome in congenital scoliosis. Recent breakthroughs in genetics related to gene and environment interactions associated with CVM development are discussed. The Klippel-Feil syndrome which is associated with cervical segmentation abnormalities is illustrated as an example in which animal models, such as the zebrafish, can be utilized to provide functional evidence of pathogenicity of identified mutations.

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“…Hyperthermia has been shown to induce malformations in numerous animal models and has been associated with human abnormalities, but the precise molecular mechanism(s) for translation into specific cellular functions remains largely unknown 14, 15…”

Section: Introductionmentioning

confidence: 99%

Influence of hyperthermal regimes on experimental teratoma development in vitro

Bojanac

Rogosic

Sinčić

et al. 2018

Int J Experimental Path

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SummaryWe screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air‐liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation (P ˂ .0001) and enhanced differentiation of both myotubes (P ˂ .01) and cylindrical epithelium (P ˂ .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth (P ˂ .01) and diminished cell proliferation (P ˂ .0001). Long‐term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival (P ˂ .005). Long‐term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival (P ˂ .0001), overall growth (P ˂ .01) and cartilage differentiation (P ˂ .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum‐free medium (CEM43°C 630 minutes) or treatment with an anti‐HSP70 antibody before long‐term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models.

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Hyperthermia: malformations to chaperones

Cited by 31 publications

References 130 publications

Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy

Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy

Clinical, Genetic and Environmental Factors Associated with Congenital Vertebral Malformations

Influence of hyperthermal regimes on experimental teratoma development in vitro

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