Low-activity programming of the PDGFRβ/FAK pathway mediates H-type vessel dysplasia and high susceptibility to osteoporosis in female offspring rats after prenatal dexamethasone exposure

摘要: Abstract Dexamethasone is a common synthetic glucocorticoid drug that can promote foetal lung maturity. An increasing number of studies have shown prenatal dexamethasone exposure (PDE) cause variety short-term and long-term hazards to offspring, including bone development toxicity. H-type vessels are newly discovered subtype blood associated with promoted formation maintenance mass. In this study, we aimed explore whether involved in PDE-induced long toxicity offspring its mechanism. vivo, injected (0.2 mg/kg.d) subcutaneously at gestational days 9–20 observed the vessel abundance mass different time points rats. vitro, investigated effect (0, 20, 100, 500 nM) on tube function rat marrow-derived endothelial progenitor cells (EPCs) explored Our results showed adult PDE female rats were susceptible osteoporosis. addition, inhibited mass, expression platelet-derived growth factor receptor β (PDGFRβ)/focal adhesion kinase (FAK) pathway-related genes antenatal postnatal offspring. Moreover, (GR), CCAAT enhancer binding protein α (C/EBPα) miR-34c foetuses. suppressed EPCs activity PDGFRβ/FAK pathway, which was mediated by GR/C/EBPα/miR-34c signalling activation. summary, dysplasia high susceptibility osteoporosis mechanism related low-activity programming pathway induced This study enhances understanding molecular dexamethasone-induced provides new insights for exploring early intervention therapeutic targets foetal-derived