Skip to Main content Skip to Navigation
New interface
Journal articles

The low‐expression programming of 11β‐HSD2 mediates osteoporosis susceptibility induced by prenatal caffeine exposure in male offspring rats

Abstract : Background and Purpose Prenatal caffeine exposure (PCE) can cause developmental toxicity of long bones in offspring, but the long-term effects and the underlying mechanism have not been fully clarified. Here, we investigated the effects of PCE peak bone mass accumulation and osteoporosis susceptibility in offspring and its intrauterine programming mechanism. Experimental Approach Pregnant Wistar rats were administrated intragastrically with saline or caffeine (120 mg·kg−1·day−1) on gestational days 9–20. The serum and bone samples were collected from the fetal and postnatal offspring for bone mass, genes expression and corticosterone analysis. Then, rat bone marrow mesenchymal stem cells (BMSCs) were treated with corticosterone in vitro to confirm the molecular mechanism. Key Results PCE caused fetal bone dysplasia in male and female offspring. In adulthood, PCE reduced peak bone mass and increased osteoporosis susceptibility in male offspring but not in females. Meanwhile, PCE only decreased the H3K9ac and expression levels of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) before and after birth in the male offspring but not in the females. Moreover, the high level of corticosterone induced by PCE down-regulated the H3K9ac and expression levels of 11β-HSD2 through promoting glucocorticoid receptor (GR; NR3C1) into the nucleus of bone marrow mesenchymal stem cells (BMSCs) and recruiting histone deacetylase 11 (HDAC11) binding to 11β-HSD2 promoter region, which further enhanced the effect of corticosterone on suppressing osteogenic function of BMSCs. Conclusion and Implications PCE caused osteoporosis susceptibility in male adult offspring, which attributed to the low-functional programming of 11β-HSD2 induced by corticosterone via GR/HDAC11 signalling.
Document type :
Journal articles
Complete list of metadata

https://hal.univ-lorraine.fr/hal-02969242
Contributor : Céline Huselstein Connect in order to contact the contributor
Submitted on : Friday, October 16, 2020 - 2:43:02 PM
Last modification on : Tuesday, May 10, 2022 - 3:18:10 PM

Intranet access

Identifiers

Citation

Hao Xiao, Zhixin Wu, Bin Li, Yangfan Shangguan, Jean‐françois Stoltz, et al.. The low‐expression programming of 11β‐HSD2 mediates osteoporosis susceptibility induced by prenatal caffeine exposure in male offspring rats. British Journal of Pharmacology, 2020, 177 (20), pp.4683-4700. ⟨10.1111/bph.15225⟩. ⟨hal-02969242⟩

Share

Metrics

Record views

26