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Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT
- Source :
- Environment International, Environment International, Elsevier, 2021, 157, ⟨10.1016/j.envint.2021.106822⟩, Environment International, Vol 157, Iss, Pp 106822-(2021), Environment International, 2021, 157, ⟨10.1016/j.envint.2021.106822⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- Author(s): Chamorro-Garcia, Raquel; Poupin, Nathalie; Tremblay-Franco, Marie; Canlet, Cecile; Egusquiza, Riann; Gautier, Roselyne; Jouanin, Isabelle; Shoucri, Bassem M; Blumberg, Bruce; Zalko, Daniel | Abstract: BackgroundEndocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act.ObjectivesWe sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure.MethodsWe used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat.ResultsMetabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation.DiscussionThis study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.
- Subjects :
- Male
[SDV]Life Sciences [q-bio]
Physiology
Disease
Endocrine Disruptors
Metabolic disruptor
Oral and gastrointestinal
mycotoxin
chemistry.chemical_compound
Mice
0302 clinical medicine
Pregnancy
2.1 Biological and endogenous factors
Obesogen
GE1-350
Aetiology
General Environmental Science
0303 health sciences
Liver Disease
Tributyltin
3. Good health
[SDV] Life Sciences [q-bio]
Endocrine disruptor
post-harvest disease
Female
Pediatric Research Initiative
aggressiveness factor
Biology
03 medical and health sciences
Metabolomics
Insulin resistance
medicine
Metabolome
Animals
Obesity
Penicillium expansum
patulin
Metabolic and endocrine
apples
030304 developmental biology
Nutrition
Prevention
medicine.disease
Estrogen
Environmental sciences
chemistry
Transgenerational effects
Trialkyltin Compounds
Digestive Diseases
030217 neurology & neurosurgery
Environmental Sciences
Subjects
Details
- Language :
- English
- ISSN :
- 01604120
- Database :
- OpenAIRE
- Journal :
- Environment International, Environment International, Elsevier, 2021, 157, ⟨10.1016/j.envint.2021.106822⟩, Environment International, Vol 157, Iss, Pp 106822-(2021), Environment International, 2021, 157, ⟨10.1016/j.envint.2021.106822⟩
- Accession number :
- edsair.doi.dedup.....de2ee96b85455345dcb075add2595f9e