What is it about?
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, whereMMIis 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 stagesof development. In hens,MMIwas 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 3,5,30-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 onlymoderately 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.
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Why is it important?
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.
Perspectives
Taken together, our data show that long-term MMI treatment of hens severely reduces T4 production in the thyroid gland but induces a relative increase in thyroidal T3 content. As a result, peripheral tissues can maintain normal T3 levels, but the brain is clearly hypothyroid. As in mammals, the treatment leads to the maternal transfer of MMI and its oxidised metabolites to the developing embryo. Levels in embryonic tissues are relatively high, especially at the early stages, and MMI and/or its oxidised metabolites may therefore have cytotoxic effects on all developing tissues including the brain. Long-term MMI treatment also reduces TH availability in the egg yolk, resulting in lower T3 availability in the early embryonic brain. At later stages, the maternally derived MMI also disturbs embryonic thyroid gland function. Combined with the lower TH content of the yolk, this results in a reduced T3 content in the peripheral tissues and brain of 14-day-old embryos and in the brain of 18-day-old embryos. We can conclude that the maternal transfer of MMI and its metabolites to the embryo can be harmful for embryonic development, in particular, for the brain, by a combination of anti-thyroidal and possibly local cytotoxic effects, an observation that may also be of relevance to the human situation.
Full Professor Ahmed R. G.
Division of Anatomy and Embryology, Zoology department, Faculty of Science, Beni-Suef University, Egypt.
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This page is a summary of: Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues, Journal of Endocrinology, April 2013, Bioscientifica,
DOI: 10.1530/joe-13-0089.
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