Low perinatal caffeine intake alters offspring thyroid function in a sex- and age-dependent manner

During perinatal period, some women limit caffeine intake to 300mg/day, following the WHO recommendation. Previously, using an animal model of low perinatal caffeine exposure, correspondent to 250mg/day for human, we observed a deleterious effect on thyroid hormone (TH), with low total T3 in dams and weaned male pups and high T3 in adult offspring of both sexes. The hypothesis of the present study is that this phenotype results from alterations in TH synthesis and metabolism. Pregnant Wistar rats received vehicle or caffeine (CAF, 25mg/kg/day) by gavage during gestation and lactation. We evaluated markers of TH synthesis in dams and offspring, such as gland morphology and mRNA expression. Here, at birth, CAF males presented higher total T4 (+96%; P < .05) and unchanged total T3 and TSH. At weaning, CAF dams presented only lower TSH. CAF male offspring presented lower colloid area, CAF female offspring presented greater thyroid epithelial height, and both sexes presented unchanged mRNA expression of TH synthesis markers, such as thyroid stimulating hormone receptor (Tshr), sodium-iodine symporter (Nis), thyroperoxidase (Tpo), dual oxidase (Duox), NADP oxidase 2 (Nox2) and iodothyronine deiodinase 1 (Dio1). Adult CAF males presented greater epithelial area, downregulation of Nis mRNA expression, and higher hepatic Dio1 mRNA expression. However, CAF females presented higher TSH, although genes of TH synthesis were downregulated. Perinatal low caffeine exposure promotes temporal adaptive changes in the pituitary-thyroid axis, thyroid gland and peripheral TH metabolism of offspring, supporting our hypothesis. These modifications contribute to changes in TH levels in an age- and sex-dependent manner.