RGD Reference Report - Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation. - Rat Genome Database

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Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation.

Authors: Tan, Y  Liu, J  Deng, Y  Cao, H  Xu, D  Cu, F  Lei, Y  Magdalou, J  Wu, M  Chen, L  Wang, H 
Citation: Tan Y, etal., Toxicol Lett. 2012 Nov 15;214(3):279-87. doi: 10.1016/j.toxlet.2012.09.007. Epub 2012 Sep 17.
RGD ID: 8661261
Pubmed: PMID:22995397   (View Abstract at PubMed)
DOI: DOI:10.1016/j.toxlet.2012.09.007   (Journal Full-text)

Several epidemiological investigations, including previous work by our laboratory, indicate that maternal caffeine consumption is associated with intrauterine growth retardation and impaired fetal length growth. Skeletal development is critical for length growth. In the present study, our goals were to determine the effects of prenatal caffeine exposures on fetal skeletal growth and to investigate the mechanisms associated with such effects. Pregnant Wistar rats were injected intragastrically with 120mg/kg of caffeine intragastrically each day from gestational days 11-20. Maternal prenatal caffeine exposure was associated with decreased fetal femur lengths and inhibited of synthesis of extracellular matrices in fetal growth plates Moreover, caffeine exposure significantly increased the levels of fetal blood corticosterone and decreased IGF-1mRNA expression levels in the liver and growth plate. The expression levels of IGF-1 signaling pathway components (IGF-1R, IRS-1, AKT1/2 and Col2A1) were also reduced. In addition, the results of chromatin immunoprecipitation assays indicated that caffeine exposure down-regulated histone methylation of fetal IGF-1 in the liver. These results suggest that prenatal caffeine exposure may inhibit fetal skeletal growth through a mechanism that is associated with increased fetal exposure to maternal glucocorticoids and results in lower IGF-1 signaling pathway activity. Taken together, these results raise important concerns regarding the skeletal growth toxicity of caffeine and potentially indicate the intrauterine origins of adult osteoporosis and osteoarthritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Fetal Growth Retardation  ISOCol2a1 (Rattus norvegicus)8661261; 8661261mRNA:decreased expression:distal epiphyseal plate of femur (rat)RGD 
Fetal Growth Retardation  IEP 8661261mRNA:decreased expression:distal epiphyseal plate of femur (rat)RGD 
Fetal Growth Retardation  ISOIrs1 (Rattus norvegicus)8661261; 8661261mRNA and protein:decreased expression:growth plate:RGD 
Fetal Growth Retardation  IEP 8661261mRNA and protein:decreased expression:growth plate:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to caffeine  IEP 8661261; 8661261 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Col2a1  (collagen type II alpha 1 chain)
Igf1  (insulin-like growth factor 1)
Irs1  (insulin receptor substrate 1)

Genes (Mus musculus)
Col2a1  (collagen, type II, alpha 1)
Irs1  (insulin receptor substrate 1)

Genes (Homo sapiens)
COL2A1  (collagen type II alpha 1 chain)
IRS1  (insulin receptor substrate 1)


Additional Information