title: Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues.
abstract: Methimazole (MMI) is an anti-thyroid drug used in the treatment of chronic hyperthyroidism. There is, however, some debate about its use during pregnancy as MMI is known to cross the mammalian placenta and reach the developing foetus. A similar problem occurs in birds, where MMI is deposited in the egg and taken up by the developing embryo. To investigate whether maternally derived MMI can have detrimental effects on embryonic development, we treated laying hens with MMI (0.03% in drinking water) and measured total and reduced MMI contents in the tissues of hens and embryos at different stages of development. In hens, MMI was selectively increased in the thyroid gland, while its levels in the liver and especially brain remained relatively low. Long-term MMI treatment induced a pronounced goitre with a decrease in thyroxine (T₄) content but an increase in thyroidal 3,5,3'-triiodothyronine (T₃) content. This resulted in normal T₃ levels in tissues except in the brain. In chicken embryos, MMI levels were similar in the liver and brain. They gradually decreased during development but always remained above those in the corresponding maternal tissues. Contrary to the situation in hens, T₄ availability was only moderately affected in embryos. Peripheral T₃ levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T₃ content was decreased at all embryonic stages tested. We conclude that all embryonic tissues are exposed to relatively high doses of MMI and its oxidised metabolites. The effect of maternal MMI treatment on embryonic thyroid hormone availability is most pronounced for brain T₃ content, which is reduced throughout the embryonic development period.
authors.affiliation: Laboratory of Comparative Endocrinology, Department of Biology, KU Leuven, Naamsestraat 61, PB 2464, B-3000 Leuven, Belgium.
authors.forename: Stijn L J
authors.initials: SL
authors.lastname: Van Herck
authors.forename: Stijn
authors.initials: S
authors.lastname: Geysens
authors.forename: Edward
authors.initials: E
authors.lastname: Bald
authors.forename: Grazyna
authors.initials: G
authors.lastname: Chwatko
authors.forename: Evelyne
authors.initials: E
authors.lastname: Delezie
authors.forename: Elham
authors.initials: E
authors.lastname: Dianati
authors.forename: R G
authors.initials: RG
authors.lastname: Ahmed
authors.forename: Veerle M
authors.initials: VM
authors.lastname: Darras
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D004529:Egg White / Q000737:chemistry; D004530:Egg Yolk / Q000737:chemistry; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007037:Hypothyroidism / Q000139:chemically induced* / Q000196:embryology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008713:Methimazole / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D013956:Antithyroid Agents; D012333:RNA, Messenger; D013963:Thyroid Hormones; D008713:Methimazole; D007453:Iodide Peroxidase
keywords: brain; chicken; development; methimazole; thyroid hormone