title: Effect of antithyroid drug on chick embryos during the last week of development: delayed hatching and decreased cerebellar acetylcholinesterase activity.
abstract: OBJECTIVE
  Hypothyroid state during embryogenesis disturbs normal growth and brain development, influencing later life. To evaluate the harmful consequences of the state during embryogenesis using an animal model, we inhibited thyroid hormone biosynthesis in chick embryos by using methimazole (MMI).
  
  
  METHODS
  Typically, embryos were treated with MMI (20 µmol/egg) on day 14, and examined on specific days.
  
  
  RESULTS
  Of the control embryos, 94% hatched on day 21, whereas 0% and 60% of MMI-treated embryos hatched on days 21 and 24, respectively. MMI retarded the rates of bodyweight gain as well as liver and heart development, and delayed hatching. However, the external differences in appearance and differences in the weights of the newly hatched control chicks on day 21 and the MMI-treated chicks on day 24 were less obvious. Embryos treated with MMI exhibited increased mass in their brain parts on day 24. Most notably, the treatment resulted in a 1.35-fold increase in cerebellum weight compared to that of the untreated animals. Acetylcholinesterase activity in the cerebellum on the day of hatching decreased significantly to 0.85-fold that of the untreated controls. Thyroid hormone receptor β mRNA was detected from day 12 and dramatically expressed from day 19 to the day of hatching.
  
  
  CONCLUSIONS
  The 'fertilized hen's egg-chick embryo-chick system' is an appropriate animal model for investigating the hypothyroid state during embryogenesis. Decreased cerebellar acetylcholinesterase activity after MMI treatment was assumed to relate to a mechanism of motor and cognitive deficits in congenital hypothyroidism.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine             Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University, Shiwa-Gun, Iwate, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Haba
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishigori
authors.forename: Yu
authors.initials: Y
authors.lastname: Tezuka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kagami
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Hideo
authors.initials: H
authors.lastname: Nishigori
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D002642:Chick Embryo; D047108:Embryonic Development / Q000187:drug effects*; D008713:Methimazole / Q000494:pharmacology*
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D000110:Acetylcholinesterase