Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.
Fiche publication
Date publication
octobre 2015
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MAGDALOU Jacques
Tous les auteurs :
Ni Q, Tan Y, Zhang X, Luo H, Deng Y, Magdalou J, Chen L, Wang H
Lien Pubmed
Résumé
Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.
Mots clés
Alcohol Drinking, adverse effects, Animals, Cartilage, Articular, pathology, Corticosterone, blood, Disease Susceptibility, Ethanol, toxicity, Female, Fetal Growth Retardation, blood, Insulin-Like Growth Factor I, metabolism, Joints, pathology, Male, Osteoarthritis, blood, Pregnancy, Prenatal Exposure Delayed Effects, blood, Rats, Wistar, Running, Signal Transduction
Référence
Sci Rep. 2015 Oct 5;5:14711