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Intrauterine Programming of Glucocorticoid–Insulin-Like Growth Factor-1 Axis–Mediated Developmental Origin of Osteoporosis Susceptibility in Female Offspring Rats with Prenatal Caffeine Exposure

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Shangguan, Yangfan | Wen, Yinxian | Tan, Yang | Qin, Jun | Jiang, Hongqiang | Magdalou, Jacques | Chen, Liaobin | Wang, Hui

Edité par CCSD ; American Society for Investigative Pathology / Elsevier -

International audience. Epidemiologic investigations suggest that excessive intake of caffeine during pregnancy is one of therisk factors for osteoporosis in adult offspring. However, the phenomena and mechanisms haveremained obscure. This study found that prenatal caffeine exposure (PCE) leads to persistent bonedysplasia in gestational day 20 and postnatal week 12 offspring rats and increases the susceptibility toosteoporosis in postnatal week 28 offspring rats. In the embryonic period, PCE increases the concen-tration of serum corticosterone and inhibits the expression of insulin-like growth factor-1 (IGF1) andosteogenic differentiation genes. After birth, the recovery of IGF1 expression in PCE offspring is unableto completely compensate osteogenic function, and chronic stress can lead to a further decrease in IGF1expression. In vitro experiments found that corticosterone instead of caffeine restrains mineralizednodule formation and osteoblast differentiation by inhibiting IGF1 expression. The corticosteroneinhibits H3K9 and H3K14 histone acetylation of IGF1 in osteoblasts through glucocorticoid receptor andCCAAT and enhancer binding protein a, respectively. In conclusion, glucocorticoid instead of caffeineinhibits bone IGF1 expression via glucocorticoid receptor and CCAAT and enhancer binding protein aand mediates the PCE-induced bone dysplasia and bone mass reduction in offspring fetal rats, whichmay contribute to osteoporosis susceptibility in adulthood.

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