Postnatal hypothyroidism in mice leads to developmental delays and metabolic dysfunction in the male offspring, according to a study recently published in Endocrinology.
Researchers led by Karine Gauthier, PhD, of the L’Institut de Génomique Fonctionnelle de Lyon, in Lyon, France, point out that thyroid hormones (TH) play an important role in the development of organs – the brain, bones, intestines, and brown adipose tissue. The authors write that in mice, for most of the pregnancy, the fetus relies on maternal TH and begins to produce its own TH just before birth.
“In humans, up to 10% of the pregnancies is associated with hypothyroidism (0.5% – 3% overt and 2% – 10% subclinical),” the authors continue. “An immediate supplementation of TH at birth can avoid developmental consequences in the newborn. However, if not corrected this gestational hypothyroidism correlates with higher frequency of metabolic diseases in the euthyroid adults. No causative role of hypothyroidism has been established yet.”
In “Postnatal exposure to maternal hypothyroidism leads to developmental delay and metabolic dysregulations in male mice,” Gauthier and her colleagues set out to determine in mice whether short windows of maternal hypothyroidism either during gestation or in the two first weeks of lactation had an effect on the development of their pups and most importantly on their sensitivity to metabolic dysregulation later in life.
. “An immediate supplementation of TH at birth can avoid developmental consequences in the newborn. However, if not corrected this gestational hypothyroidism correlates with higher frequency of metabolic diseases in the euthyroid adults. No causative role of hypothyroidism has been established yet.”
The researchers induced perinatal hypothyroidism in one-third of the female mice and gave mouse pups one day after birth born from hypothyroid mothers (pre-HT) to euthyroid mothers, and vice versa. “Animals from the CTRL group were born and raised by euthyroid mothers,” the authors write.
“In this study, we used animals exposed to maternal hypothyroidism during either gestation or their [two] first weeks of life to assess both the developmental and the long-term consequences of the [two] short perinatal periods of hypothyroidism,” the authors continue.
What Gauthier and her team found was those pups born to mothers with hypothyroidism normalized thyroid hormones and development two weeks after birth. “In contrast,” the authors write, “transient hypothyroidism, limited to the first [three] postnatal weeks, has severe consequences on developmental processes.”
The researchers acknowledge the limitations of the study: only male pups were used, whereas hormonal and metabolic regulations are recognized to be sexually dimorphic. “Metabolic changes were inferred from altered expression of metabolic genes, direct measurement would reinforce our conclusions,” they write. The authors also note that extrapolation of the results of the animal study since the timing of human and TH production is much different from mice. “However, our data clearly establish that T3 does participate to this early programing at least in mice,” the authors conclude. “Perturbation of T3 signaling during this early period via endocrine disruptors or other, could have long-term consequences not only on brain function but also on sensitivity to metabolic diseases.”
