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Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment
Ifigeneia Kassotaki1, Georgios Valsamakis2,3, George Mastorakos4
1Department of Internal Medicine, 2nd Internal Medicine Clinic, Venizeleio Pananeio General Hospital, Heraklion, Greece.
Insights
Prenatal stress impacts fetal brain development by altering stress hormone regulation. Epigenetic changes from stress can lead to long-term health issues and increased disease susceptibility in offspring.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Early life insults disrupt development, increasing disease susceptibility.
- Prenatal stress affects offspring neurodevelopment via maternal hypothalamic-pituitary-adrenal (HPA) axis dysregulation.
Purpose of the Study:
- To review the role of corticotropin-releasing hormone (CRH) and stress mediators in fetal neurodevelopment.
- To explore how prenatal stress impacts brain development and long-term health outcomes.
Main Methods:
- Literature review of studies on prenatal stress, HPA axis, CRH, and neurodevelopment.
- Analysis of research on epigenetic modifications in the fetal brain due to stress.
Main Results:
- Maternal stress responses alter offspring neurodevelopmental trajectories.
- Increased stress hormones are linked to structural brain changes and altered neuronal signaling.
- Epigenetic changes, such as gene methylation, act as molecular memories of stress exposure.
Conclusions:
- CRH and glucocorticoids are key regulators of fetal neurodevelopment.
- Prenatal stress can lead to lasting modifications in offspring stress regulation and increased psychosomatic disorder risk.
- Epigenetic programming by stress plays a crucial role in fetal development and long-term health.
Abstract:
Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother's hypothalamic-pituitary-adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring's stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.
