Potential teratogenic effect of prenatal dexamethasone administration on palate development: Experimental study in rats

Wafaa Yahia Alghonemy , Abdelmonem Awad Hegazy , Fayig Elmigdadi , Gamal Abdel Nasser Atia , Mai Badreldin Helal
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Abstract

Background

The interaction of cell populations and synchronization of cell signaling pathways during craniofacial development can cause malformations such as facial clefts when interrupted by teratogenic agents including synthetic corticosteroids. Therefore, this study aimed to determine the potentially disturbing dexamethasone (Dex) effect on palatal shelf development in rat embryos and the possible reasons for this teratogenic potential in relation to fibroblast growth factor 10 (FGF10) as well as FGF10 receptor2 (FGFR2) signaling.

Methods

Thirty pregnant rats were used, which were then randomly categorized into three groups of ten animals each: the control group, where pregnant rats received no treatment, Sham group in which pregnant rats were injected subcutaneously with saline (0.4 mg/kg body weight) during the mid-pregnancy period at gestational day 9–14, and Dex-treated group, where pregnant rats received 0.4 mg/kg of Dex at mid-gestational period. Pregnant animals from all groups were sacrificed on day 20 of gestation before birth and the fetuses were removed for examination of the palatal shelves using a light microscope (LM). In addition, a real-time polymerase chain reaction and a reverse transcription-polymerase chain reaction (RT-PCR) were done to evaluate FGF10 and its receptor FGFR2 gene expression.

Results

The cleft palate incidence rates in the groups of embryos were determined. Only the offspring in the Dex group showed a cleft palate. Moreover, the cleft palate incidence rate in the Dex group was significantly different compared to controls. Moreover, a significant decrease in FGF10 and FGFR2 expression levels was reported in the Dex group than in the controls.

Conclusions

Dex treatment in mid-gestation may increase the incidence of cleft palate development, which may be due to modulation of FGF signaling. This calls for caution when using this medication in the first half of pregnancy unless absolutely necessary and under close medical supervision.

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产前服用地塞米松对上颚发育的潜在致畸作用:大鼠实验研究
背景在颅面部发育过程中,细胞群的相互作用和细胞信号通路的同步化在受到包括合成皮质类固醇在内的致畸剂干扰时会导致畸形,如面裂。因此,本研究旨在确定地塞米松(Dex)对大鼠胚胎腭架发育的潜在干扰作用,以及与成纤维细胞生长因子 10(FGF10)和 FGF10 受体 2(FGFR2)信号传导有关的致畸可能原因。方法使用 30 只孕鼠,然后将其随机分为三组,每组 10 只:对照组,孕鼠不接受任何治疗;Sham 组,孕鼠在妊娠中期的第 9-14 天皮下注射生理盐水(0.4 毫克/千克体重);Dex 治疗组,孕鼠在妊娠中期接受 0.4 毫克/千克的 Dex。各组孕鼠均于妊娠第 20 天在出生前处死,取出胎儿用光学显微镜(LM)检查腭骨架。此外,还进行了实时聚合酶链反应和反转录聚合酶链反应(RT-PCR),以评估 FGF10 及其受体 FGFR2 基因的表达。只有 Dex 组的后代出现了腭裂。此外,与对照组相比,Dex组的腭裂发生率有显著差异。结论 在妊娠中期进行地塞米松治疗可能会增加腭裂的发生率,这可能是由于地塞米松调节了生长因子信号转导。因此,除非万不得已,在医生的密切监护下,否则在妊娠前半期使用这种药物时应谨慎。
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来源期刊
CiteScore
2.90
自引率
0.00%
发文量
71
审稿时长
25 days
期刊介绍: Translational Research in Anatomy is an international peer-reviewed and open access journal that publishes high-quality original papers. Focusing on translational research, the journal aims to disseminate the knowledge that is gained in the basic science of anatomy and to apply it to the diagnosis and treatment of human pathology in order to improve individual patient well-being. Topics published in Translational Research in Anatomy include anatomy in all of its aspects, especially those that have application to other scientific disciplines including the health sciences: • gross anatomy • neuroanatomy • histology • immunohistochemistry • comparative anatomy • embryology • molecular biology • microscopic anatomy • forensics • imaging/radiology • medical education Priority will be given to studies that clearly articulate their relevance to the broader aspects of anatomy and how they can impact patient care.Strengthening the ties between morphological research and medicine will foster collaboration between anatomists and physicians. Therefore, Translational Research in Anatomy will serve as a platform for communication and understanding between the disciplines of anatomy and medicine and will aid in the dissemination of anatomical research. The journal accepts the following article types: 1. Review articles 2. Original research papers 3. New state-of-the-art methods of research in the field of anatomy including imaging, dissection methods, medical devices and quantitation 4. Education papers (teaching technologies/methods in medical education in anatomy) 5. Commentaries 6. Letters to the Editor 7. Selected conference papers 8. Case Reports
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