Maternal nutrient deprivation induces sex‐specific changes in thyroid hormone receptor and deiodinase expression in the fetal guinea pig brain

Abstract

Thyroid hormone deprivation during fetal life has been implicated in neurodevelopmental morbidity. In humans, poor growth in utero is also associated with fetal hypothyroxinaemia. In guinea pigs, a short period (48 h) of maternal nutrient deprivation at gestational day (gd) 50 results in fetuses with hypothyroxinaemia and increased brain/body weight ratios. Thyroid hormone action is mediated by nuclear thyroid hormone receptors (TRs) and is dependent upon the prereceptor regulation of supply of triiodothyronine (T 3 ) by deiodinase enzymes. Examination of fetal guinea pig brains using in situ hybridization demonstrated widespread expression of mRNAs encoding TRα1, α2 and β1, with regional colocalization of deiodinase type 2 (D2) mRNA in the developing forebrain, limbic structures, brainstem and cerebellum at gd52. With maternal nutrient deprivation, TRα1 and β1 mRNA expression was significantly increased in the male, but decreased in the female fetal hippocampus and cerebellum and other areas showing high TR expression under euthyroid conditions. Maternal nutrient deprivation resulted in elevated D2 mRNA expression in males and females. Deiodinase type 3 (D3) mRNA expression was confined to the shell of the nucleus accumbens, the posterior amygdalohippocampal area, brainstem and cerebellum, and did not change with maternal nutrient deprivation. In conclusion, maternal nutrient deprivation resulted in sex-specific changes in TR mRNA expression and a generalized increase in D2 mRNAs within the fetal brain. These changes may represent a protective mechanism to maintain appropriate thyroid hormone action in the face of fetal hypothyroxinaemia in order to optimize brain development.

Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: A tool for examining OH-BDE toxicity to early life stages

“…In rodents, Dio3 is also expressed in placental tissues and is important in maintaining low thyroid hormone concentrations in the developing fetus (Huang et al, 2003). Up-regulation of Dio3 may lead to lower than normal T3 concentrations in the developing fetus (Chan et al, 2005). …”

Iodine Deficiency and Schooling Attainment in Tanzania

“…First, Friedhoff et al (2000) found that the effect of artificially restricting maternal thyroid hormone in utero on fetal neurodevelopment and behavioral outcomes was significantly larger in female relative to male rat progeny. Although the mechanism underlying sex-selective effects of maternal nutrient deprivation on brain development could not be directly addressed by their experiment, a recent study of gene expression in nutrient deprived fetal guinea pigs by Chan et al (2005) provides insight into the cellular pathways.…”

Iodine deficiency and women’s health: Colonialism’s malign effect on health in Oromia region, in Ethiopia

“…The effects of ID are more severe in females [24][25][26]41]. The experimental studies conducted by Chan [24] and his colleagues clearly suggest that the female fetus is more sensitive in its cognitive development to maternal ID than is the male. In developing countries, iodine deficiency is seen as an obstacle to women's achievement [42].…”

“…ID is one of the major causes of reproductive failure and mental retardation. Clinical research in ID sensitivity has made it clear that female fetuses are more sensitive than male ones [24][25][26].…”