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 (T 4 ) content but an increase in thyroidal 3,5,3 0 -triiodothyronine (T 3 ) content. This resulted in normal T 3 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, T 4 availability was only moderately affected in embryos. Peripheral T 3 levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T 3 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 T 3 content, which is reduced throughout the embryonic development period.

Experimental manipulation of food availability leads to short‐term intra‐clutch adjustment in egg mass but not in yolk androgen or thyroid hormones

“…In mammals and fish maternal thyroid hormones are crucial for normal growth, development and even survival (reviewed by Power et al , Patel et al ). The avian embryo possesses thyroid hormone receptors before starting its own thyroid hormone production (Geysens et al , Van Herck et al , ). Furthermore, experimental elevation of thyroid hormones increased growth and hatching speed in quail and chicken (Wilson and McNabb ) and body mass in pigeons and great tits Parus major (Hsu et al pers.…”

The Effects of Maternal Hyperthyroidism on Histologic Changes in Parietal Lobe in Rat Embryos

“…A shortage of thyroid hormones during the pre-birth period will lead to irreversible damage to the brain and mental retardation [14]. Madeira et al (1991) reviewed the impacts of hyperthyroidism on the granular layer of the dentate gyrus of the hippocampus in mature male and female rats.…”

“…The greatest state of hyperthyroidism is in the form of Graves' disease. Untreatedhyperthyroidism in pregnant mothers is associated with hyperthyroidism in embryos [14,15].…”

Maternal Hyperthyroidism and Developing Hematopoiesis Dysfunction

“…Maternal thyroid hormones [THs;3,5, and thyroxine (T4)] show central roles in the fetal and neonatal development during the gestation and lactation periods (El-bakry et al, 2010;Ahmed, 2011Ahmed, , 2012aAhmed, ,b, 2013Ahmed, , 2014Ahmed, , 2015aAhmed, -c, 2016aAhmed, -d, 2017aAhmed, -v, 2018aAhmed et al, 2008;2013a,b, 2014, 2015a,b, 2018aAhmed and Incerpi, 2013;Van Herck et al, 2013;El-Gareib, 2014, Incerpi et al, 2014;Candelotti et al, 2015;De Vito et al, 2015;El-Ghareeb et al, 2016;Ahmed and El-Gareib, 2017), in particular the hematopoietic cell proliferation and growth, the number of red blood cells (RBCs) and white blood cells (WBCs), and platelet counts (Grymuła et al, 2007;Kawa et al, 2010;Pascual and Aranda, 2013;Kandir and Keskin, 2016). In the bone marrow, Kendrick et al (2008) reported that THs can induce its cellular production.…”