Development of cerebral mitochondrial respiratory function is impaired by thyroid hormone deficiency before birth in a region‐specific manner

Thyroid hormones regulate adult metabolism partly through actions on mitochondrial oxidative phosphorylation (OXPHOS). They also affect neurological development of the brain, but their role in cerebral OXPHOS before birth remains largely unknown, despite increase energy demand during neonatal period. Thus, this study examined prepartum hypothyroid fetal sheep. Using respirometry, Complex I (CI), II (CII), and combined CI&CII capacity were measured cerebellum cortex at 128 142 days gestational age (dGA) after surgical thyroidectomy or sham operation 105 dGA (term ~145 dGA). Mitochondrial electron transfer system (ETS) complexes, mRNA transcripts related to biogenesis ATP production, density quantified using molecular techniques. Cerebral morphology was assessed by immunohistochemistry stereology. In cortex, hypothyroidism reduced CI-linked respiration CI abundance dGA, respectively, caused upregulation PGC1α (regulator biogenesis) thyroid hormone receptor β respectively. contrast, cerebellum, CI&II- CII-linked with no significant effect ETS complexes. addition, cerebellar glucocorticoid adenine nucleotide translocase (ANT1) downregulated These alterations function accompanied myelination. The findings demonstrate importance maturation mitochondria have implications for etiology treatment neurodevelopmental abnormalities associated human prematurity congenital hypothyroidism.