RESUMO
Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.
Assuntos
Sistema Cardiovascular/embriologia , Embrião de Mamíferos/patologia , Deficiências de Ferro , Animais , Aorta Torácica/anormalidades , Biomarcadores/metabolismo , Diferenciação Celular , Vasos Coronários/embriologia , Vasos Coronários/patologia , Suplementos Nutricionais , Edema/patologia , Embrião de Mamíferos/anormalidades , Desenvolvimento Embrionário , Feminino , Perfilação da Expressão Gênica , Interação Gene-Ambiente , Proteínas de Fluorescência Verde/metabolismo , Ferro/metabolismo , Vasos Linfáticos/embriologia , Vasos Linfáticos/patologia , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Penetrância , Fenótipo , Gravidez , Transdução de Sinais , Células-Tronco/patologia , Transgenes , Tretinoína/metabolismoRESUMO
We conducted a randomized clinical trial to compare periacetabular bone density changes after total hip arthroplasty using press-fit components with soft and hard liner materials. Bone density changes were assessed using quantitative computed tomography-assisted osteodensitometry. Twenty press-fit cups with alumina ceramic liners and 20 press-fit cups with highly cross-linked polyethylene liners were included; the nonoperated contralateral side was used as the control. Computed tomography scans were performed postoperatively and 1 year after the index operation. At the 1-year followup, we found no differences of periacetabular bone density changes between the alumina and polyethylene liner cohorts. However, we observed marked periacetabular cancellous bone density loss (up to -34%) in both cohorts. In contrast, we observed only moderate cortical bone density changes. The decrease of periacetabular cancellous bone density with retention of cortical bone density after THA suggests stress transfer to the cortical bone.