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CURATOR
A pinboard by
Emily Camm

Senior Research Associate, Univeristy of Cambridge

PINBOARD SUMMARY

I investigate how the fetal brain develops during pregnancy

Despite improvement in survival rates of children who have sustained brain injury during fetal life or just after birth, there continues to be a diverse spectrum of cognitive and motor outcomes in survivors, thus placing a substantial burden on the nation’s health and wealth. In order to develop strategies for prevention or treatment, there is a need to understand the underlying mechanisms of brain injury resulting in neurological impairment.

Mitochondria are the powerhouses of all mammalian cells, including brain cells, which rely on mitochondrial energy production for survival. Recent advances in the field of mitochondrial biology has demonstrated that mitochondrial activities go beyond supplying energy to the brain. Indeed, in the developing brain, mitochondria appear to be commanders of inflammation, cell development and connectivity, and possibly repair after injury.

In many of the key tissues essential for neonatal survival, including the brain, there are maturational changes in the fetal tissues before birth in preparation for the functional changes at delivery. Hormones play an important role in the maturation of tissues essential for neonatal survival. Cortisol, a glucocorticoid, rises in concentration in the fetus towards birth and increases the activity of the thyroid hormone, tri-iodothyronine (T3). Cortisol and T3 induce tissue-specific maturation, both in combination and independently. Fetal glucocorticoid concentrations can also rise before term in response to adverse intrauterine conditions, such as a lack of oxygen (hypoxia), whereas fetal thyroid hormones are reduced in fetuses that are growth restricted or small for gestational age. To date, little is known about the normal development of mitochondrial function in the brain during the period before birth, and how the brain mitochondria prepare for the extra demands for energy after birth.

My research aims to establish the developmental and hormone regulation of mitochondrial function in the brain, by assessing mitochondrial function in different brain regions during development, and determining whether hormones can modulate cerebral mitochondrial function. Answering these questions will provide insight into the role of mitochondria in brain development as well as injury.

6 ITEMS PINNED

Thyroid hormones in fetal growth and prepartum maturation.

Abstract: The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4 and T3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4 and T3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

Pub.: 22 Mar '14, Pinned: 03 Jul '17