Postnatal exposure to maternal hypothyroidism leads to developmental delay and metabolic dysregulations in male mice

The postnatal period of mouse development is critical for the maturation of many organs and fine tuning of hormonal feedback loops. These developmental transformations are necessary to allow the transition from a suckling pup to an independent life but they also determine the metabolic features of the adult. Thyroid hormones are key hormones that control these postnatal events. However, the impact of a short-term exposure to maternal hypothyroidism during the perinatal period on the metabolic outcome of the descendants was not clearly established. We used a new protocol to obtain animals exposed to maternal hypothyroidism only during gestation or only during their 2 first postnatal weeks. The developmental and the long-term consequences of these 2 short perinatal periods of hypothyroidism were assessed. Animals born from hypothyroid mothers did not show developmental delays. As adults, they were indistinguishable from the controls and could adequately face metabolic stresses such as exposure to a high-fat diet or cold temperature. In contrast, pups exposed to maternal hypothyroidism during lactation presented delayed growth and remained leaner than the controls. The expression of genes involved in different metabolic pathways in liver or brown adipose tissues were affected both during development and in adults. The adults were also more sensitive to diet induced obesity and to cold exposure. In conclusion, in mice, severe hypothyroidism in the pregnant dam is not detrimental for postnatal development or metabolic programing of the pups. In contrast postnatal hypothyroidism leads to developmental delays and long-lasting metabolic dysregulation in otherwise euthyroid animals.