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Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible
Yong Li1, Pablo Gonzalez, Lubo Zhang
1Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Insights
Adverse fetal stress, including exposure to glucocorticoids, can program the neonatal brain for increased vulnerability to neurological disorders later in life. Understanding these epigenetic mechanisms is key for prevention and intervention.
Area of Science:
- Neuroscience
- Developmental Biology
- Epidemiology
Background:
- Growing evidence links adverse in utero environments to later-life neurological, psychological, and psychiatric disorders.
- Fetal stresses like hypoxia, malnutrition, and substance exposure can alter brain development.
- Glucocorticoids are implicated in the epigenetic programming of fetal-origin neurological disorders.
Purpose of the Study:
- To review recent studies on the effects of fetal stress on abnormal brain development.
- To focus on the cellular, molecular, and epigenetic mechanisms involved.
- To highlight the role of glucocorticoids in programming brain vulnerability.
Main Methods:
- Review of epidemiological, clinical, and experimental studies.
- Analysis of cellular and molecular pathways.
- Focus on epigenetic modifications.
Main Results:
- Fetal stress can program heightened brain vulnerability to hypoxic-ischemic encephalopathy.
- Glucocorticoids play a central role in this programming.
- Altered brain development increases the risk of postnatal neurological diseases.
Conclusions:
- Fetal stress significantly impacts brain development and increases susceptibility to neurological disorders.
- Epigenetic mechanisms, particularly involving glucocorticoids, are crucial.
- Understanding these pathways can inform diagnosis, prevention, and intervention strategies for neonatal hypoxic-ischemic encephalopathy.
Abstract:
Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders.
