A Metabonomic Approach to Analyze the Dexamethasone‐Induced Cleft Palate in Mice

Abstract

Mice models are an important way to understand the relation between the fetus with cleft palate and changes of maternal biofluid. This paper aims to develop a metabonomics approach to analyze dexamethasone-induced cleft palate in pregnant C57BL/6J mice and to study the relationship between the change of endogenous small molecular metabolites in maternal plasma and the incidence of cleft palate. To do so, pregnant mice were randomly divided into two groups. The one group was injected with dexamethasone. On E17.5th day, the incident rates of cleft palate from embryos in two groups were calculated. The 1H-NMR spectra from the metabolites in plasma in two groups was collected at same time. Then the data were analyzed using metabonomics methods (PCA and SIMCA). The results showed that the data from the two groups displayed distinctive characters, and the incidence of cleft palate were significantly different (P < .005). To conclude, this study demonstrates that the metabonomics approach is a powerful and effective method in detecting the abnormal metabolites from mother in the earlier period of embryos, and supports the idea that a change from dexamethasone induced in maternal metabolites plays an important role in the incidence of cleft palate.

Prenatal administration of dexamethasone during early pregnancy negatively affects placental development and function in mice1

“…Previously, administration of 10 mg/kg BW of triamcinolone hexacetonide, a kind of intermediate-acting synthetic glucodorticoid, intramuscularly to ICR mice at various stages of pregnancy was shown to induce mandibular growth retardation and palatal malformation (Silbermann and Levitan 1979). More recently, C57BL/6J mice treated with 6 mg/kg BW of dexamethasone intraperitoneally at d 10 to 12 of gestation showed a signifi cantly greater incidence of cleft palate at d 17.5 of gestation (Zhou et al, 2011). Based on these previous fi ndings, we chose to use 1 and 10 mg/kg BW of dexamethasone in this study.…”

Metabolomics: Concept, methods and potential prospect in marine biology

“…Based on principle component analysis (PCA) and Soft Independent Modeling of Class Analogy (SIMCA), the result showed that the rate of uptake differed significantly in embryos with cleft palate. Zhou et al [6] demonstrates the power of the metabolomics approach in detecting abnormalities in maternal metabolites during gestation, and supports the author's hypothesis that the presence of dexamethasone in maternal metabolites contributes to the occurrence of cleft palate.…”

“…In addition, these technologies allow for simultaneous quantification of total metabolic compounds. For example, Zhou et al [6] injected dexamethasone into a group of mice at day 17.5 of pregnancy then collected 1 H-NMR spectra data for plasma metabolites. Using this data, Zhou et al [6] calculated the rate of uptake in embryos with/without cleft palate.…”

“…For example, Zhou et al [6] injected dexamethasone into a group of mice at day 17.5 of pregnancy then collected 1 H-NMR spectra data for plasma metabolites. Using this data, Zhou et al [6] calculated the rate of uptake in embryos with/without cleft palate. Based on principle component analysis (PCA) and Soft Independent Modeling of Class Analogy (SIMCA), the result showed that the rate of uptake differed significantly in embryos with cleft palate.…”

Chemical-Induced Cleft Palate Is Caused and Rescued by Pharmacological Modulation of the Canonical Wnt Signaling Pathway in a Zebrafish Model

“…All 12 teratogens induced a series of palate malformations of zebrafish palate dose-dependently, suggesting the phenotypic relevance of this zebrafish model to chemical-induced cleft palate in mammals. Moreover, IWP-L6, a specific inhibitor of the canonical Wnt signaling pathway, also induced clefting phenotypes, which were enhanced by Faiella et al, 2000;Jentink et al, 2010 Phenytoin PHT Cleft lip, tetralogy of Fallot, short neck, and diaphragmatic hernia Cleft lip and palate, congenital heart disease, and microcephaly Speidel and Meadow, 1972;Czeizel, 1976 Antithrombotic drug Warfarin WAF Maxillonasal hypoplasia and skeletal abnormalities Cleft palate, nasal hypoplasia, and skeletal abnormalities Howe and Webster, 1992;Starling et al, 2012;D'Souza et al, 2017 Antineoplastic Jordan et al, 1977;Granzow et al, 2003 Immunosuppressive drug Thalidomide THA -Limb defects, cleft lip and palate, ear defects, and small eyes Newman, 1985;Speirs, 1962;Taussig, 1962;Smithells and Newman, 1992 Anti-inflammatory drug Dexamethasone DEX Cleft lip, and cleft palate Cleft lip and palate Hviid and Mølgaard-Nielsen, 2011;Zhou et al, 2011;Kemp et al, 2016 Salicylic acid SA Cleft palate, spina bifida, cranioschisis, spondyloschisis, and abdominal fissure Neural tube defects, gastroschisis, and cleft lip/palate Trasler, 1965;Tagashira et al, 1981;Kozer et al, 2002 Non-pharmaceutical chemical Caffeine CAF Cleft palate, and digital defect Cleft palate, hydrocephalus, and interventricular septal defect Nishimura and Nakai, 1960;Collier et al, 2009 Retinoic acid RA Cleft lip and palate, ear defects, and limb and lower-body duplications Cleft palate, ear defects, hydrocephalus, and teratology of Fallot Benke, 1984;Lammer et al, 1988;Rutledge et al, 1994;Padmanabhan and Ahmed, 1997 Boric acid BA Rib defects (short rib and wavy rib) - Moore, 1997 All chemicals have been reported to induce birth defects in rodents and human.…”