Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation

Area of Science:

• Developmental neuroscience
• Stem cell biology
• Toxicology

Background:

• The developing human brain is vulnerable to thermal stress during pregnancy.
• Mechanisms of heat-induced neurodevelopmental disruption are poorly understood due to limited research models.

Purpose of the Study:

• To develop and utilize a novel brain organoid model for investigating the effects of prenatal heat exposure on human foetal brain development.
• To elucidate the molecular and cellular mechanisms underlying heat-induced neurodevelopmental alterations.

Main Methods:

• Generation of human brain organoids from pluripotent stem cells.
• Application of a periodic heating model to simulate prenatal heat exposure.
• Analysis of organoid size, neural tube development, and cell proliferation.
• Bulk RNA sequencing to identify affected signaling pathways.

Main Results:

• Periodic heat exposure caused decreased brain organoid size and impaired neural tube development.
• Heat stimulation led to abnormal WNT signaling and a reduction in G2/M progenitor cells.
• Increased neural differentiation and decreased cell proliferation were observed under heat stress.

Conclusions:

• The brain organoid model effectively recapitulates neurodevelopmental disruptions caused by prenatal heat exposure.
• Heat exposure alters critical developmental processes, including cell proliferation and differentiation, impacting brain development.
• This model serves as a valuable platform for studying maternal fever effects and potential interventions for neurodevelopmental disorders.