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

Abstract

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Correlation Between Hypothyroidism During Pregnancy and Glucose and Lipid Metabolism in Pregnant Women and Its Influence on Pregnancy Outcome and Fetal Growth and Development

“…Once hypothyroidism occurs during pregnancy, the increase of TSH level may inhibit the secretion of human chorionic gonadotropin by placenta to a certain extent, resulting in an irreversible influence on the development of placenta and fetus and damages the development of fetal nervous system ( 24 ). Moreover, long-term hypothyroidism will make the abnormal blood glucose and blood lipid levels of pregnant women for a long time, resulting in the damage of the blood vessel wall and the decrease of blood flow supply, which will further lead to the decrease of blood flow to various organs of the body, resulting in the lack of oxygen supply to cells, and, in severe cases, placenta aging will occur, resulting in the limitation of fetal growth and development ( 25 ). The above research is consistent with our results.…”

Cortisol Regulates Cerebral Mitochondrial Oxidative Phosphorylation and Morphology of the Brain in a Region-Specific Manner in the Ovine Fetus

“…A blood sample was taken from the umbilical artery before final euthanasia. Fetal brains were hemisected; fresh tissue samples (~10 mg) from the cerebrum (cerebral cortex, at the level of the ansate sulcus) and cerebellum (at the level of the horizontal fissure) were collected from the left hemisphere and placed in ice-cold buffer (miR05) [ 10 ]. The remaining portions of the left hemisphere were frozen in liquid nitrogen and stored at −80 °C for subsequent molecular analysis.…”

“…Cerebral oxygen consumption was measured by high-resolution respirometry as previously described [ 10 ]. Fresh brain samples (~10 mg) were homogenised in miR05 and transferred into oxygraph chambers (Oxygraph 2k, Oroboros Instruments, Innsbruck, Austria).…”

“…Respiration rates were corrected for citrate synthase (CS) activity. Flux control ratios (FCRs) were calculated [ 10 ] as follows: The fraction of OXPHOS capacity dissipated in the leak state: C L /CI&CII P ; OXPHOS coupling efficiency for CI-linked substrates, which represents the net OXPHOS capacity, corrected for leak respiration (CI L ): 1-CI L /CI P ; …”

Hormonal Regulation of Oxidative Phosphorylation in the Brain in Health and Disease

“…Thyroidectomized fetal sheep were characterized by diminished complex I-linked respiration and complex I abundance and, as a compensatory mechanism, enhanced PGC1α expression simultaneously with thyroid hormone receptor β upregulation in the cortex, while in the cerebellum, hypothyroidism reduced complex I, II and complex II-linked respiration with no impact on ETS complexes. The observed changes in mitochondrial processes were correlated with weakened myelination, which may cause neurodegenerative changes [ 79 ]. Additionally, a study on rodents showed a decrease in the OXPHOS rate (when NADH-generating substrates were added) and complex I and III activity in the cerebral cortex and striatum of hypothyroid Wistar rat neonates but not in the hippocampus, cerebellum, thalamus, mid brain or brain stem [ 80 ].…”