• [Show abstract] [Hide abstract]
    ABSTRACT: While methimazole (MMI) is widely used in the therapy for hyperthyroidism, several groups have reported that maternal exposure to MMI results in a variety of congenital anomalies, including choanal and esophageal atresia, iridic and retinal coloboma, and delayed neurodevelopment. Thus, adverse effects of maternal exposure to MMI on fetal development have long been suggested; however, direct evidence for the teratogenicity of MMI has not been presented. Therefore, we studied the effects of MMI on early development by using zebrafish as a model organism. The fertilized eggs of zebrafish were collected immediately after spawning and grown in egg culture water containing MMI at various concentrations. External observation of the embryos revealed that exposure to high concentrations of MMI resulted in loss of pigmentation, hypoplastic hindbrain, turbid tissue in the forebrain, swelling of the notochord, and curly trunk. Furthermore, these effects occurred in a dose-dependent manner. Precise observation of the serial cross-sections of MMI-exposed embryos elucidated delayed development and hypoplasia of the whole brain and spinal cord, narrowing of the pharynx and esophagus, severe disruption of the retina, and aberrant structure of the notochord. These neuronal, pharyngeal, esophageal, and retinal anomalous morphologies have a direct analogy to the congenital anomalies observed in children exposed to MMI in utero. Here, we show the teratogenic effects of MMI on the development of zebrafish and provide the first experimental evidence for the connection between exposure to MMI and human MMI embryopathy.
    Birth Defects Research Part B Developmental and Reproductive Toxicology 04/2013; · 1.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastroschisis is a major malformation which requires immediate surgical care to return the exposed viscera to the abdominal cavity, parenteral nutrition until bowel motility permits oral feedings, and evaluation for coexisting malformations. Almost all cases are diagnosed prenatally using midtrimester ultrasound and maternal serum alphafetoprotein measurement. This allows most infants to be delivered in a tertiary care facility where the best mode of delivery and neonatal management can be determined. About 10% of infants with gastroschisis will have other malformations. Half of these are considered related to the gastroschisis (intestinal atresia or stenosis, malrotation, cryptorchidism, amyoplasia, urinary tract obstruction). Other associated malformations occur which are not recognized to be secondary to the gastroschisis. Prominent among these are cardiac and limb defects. Fetal and neonatal mortality are increased, but neither appear related to lethal malformations. © 2008 Wiley-Liss, Inc.
    American Journal of Medical Genetics Part C Seminars in Medical Genetics 08/2008; 148C(3):219 - 230. · 4.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ocular coloboma is a developmental anomaly of the eye that results from incomplete closure of the optic fissure, occurring 5-7 weeks post conception. Congenital colobomata are important causes of childhood visual impairment and blindness. This defect typically affects the iris, cornea, ciliary body, zonules, retina, choroid and optic nerve. Colobomata can be seen in isolation and in combination with an impressive number of multisystem disorders. As yet, no effective treatment is available for this condition and management is only supportive. Based upon animal studies of coloboma, mendelian genetic disorders and chromosomal abnormalities, the molecular and genetic mechanisms that regulate optic fissure morphogenesis are now being discovered. Defining the genes and environmental factors involved in coloboma formation will aid in the development of potential therapies for patients with this malformation. This review explores the progress in understanding the clinical and molecular aspects of ocular coloboma.
    Expert Review of Ophthalmology 11/2006; 1(2):209-227.