we show for the first time that repeated administration of KI at 1 mg/kg/24h doesn't cause modification of thyroid hormones level, but leads to a reversible modification of the expression of genes involved in the synthesis and secretion of thyroid hormones.

Protracted radioiodine release, may requires repeated intake of potassium iodide (KI) to protect thyroid gland. It is well established that iodine excess inhibits transiently the thyroid function. As developing foetus depends on maternal thyroid hormones (TH) supply, more knowledge are needed about the plausible effects that repeated KI intake can cause in this sensitive population, especially that even subtle variation of maternal thyroid function may have persistent consequences on progeny brain processing. The aim of this study is to assess 1 ACCEPTED MANUSCRIPT the conséquences of repeated intake of KI during pregnancy on the progeny's thyroid function and brain development. To do so pregnant Wistar rats received KI over eight days, and then thirty days after the weaning, male progeny was subjected to behaviour test. Pituitary and thyroid hormones level, anti-thyroid antibodies level, organs morphology, genes expression and global DNA methylation were assessed. Thirty days after the weaning, KI-exposed male progeny showed an uncommon hormonal status, characterized by a decrease of both TSH (-28%) and FT4 (-7%) levels. Motor coordination was altered in KI-exposed male progeny, at the cerebellar level we observed a decrease of mRNA expression of DCX (-42%) and RC3 (-85%), on the other hand at the cortical level mRNA expression of MBP (+71%), MOBP (+90%) and Kcna1 (+42%) was increased. To conclude, repeated KI prophylaxis is not adequate during pregnancy since it led to long-term irreversible neurotoxicity in the male progeny.

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Single dose of potassium iodide (KI) is recommended to prevent the risk of thyroid cancer during nuclear accidents. However in the case of repeated/protracted radioiodine release, a unique dose of KI may not protect efficiently the thyroid against the risk of further developing a radiation-induced cancer. The new WHO guidelines for the use in planning for and responding to radiological and nuclear emergencies identify the need of more data on this subject as one of the four research priorities. The aims of the PRIODAC project are (1) to assess the associated side effects of repeated intakes of KI, (2) to better understand the molecular mechanisms regulating the metabolism of iodine, (3) to revise the regulatory French marketing authorization of 65-mg KI tablets and (4) to develop new recommendations related to the administration of KI toward a better international harmonization. A review of the literature and the preliminary data are presented here.