Perinatal hypoxia, resulting from insufficient oxygen supply to the brain around the time of birth, is
a medical emergency that can lead to hypoxic-ischemic encephalopathy (HIE). This pathology is one of the leading causes of mortality and neurological disability in newborns. Surviving children may have lasting sequelae, ranging from motor and cognitive disorders to learning or behavioral deficits.
Several observations indicate better prognoses for girls than for boys. However, the underlying cellular and molecular mechanisms remain largely unknown.
Human brain organoids represent relevant models for studying hypoxic responses based on sex. In a study published in iScience, researchers from the LENIT laboratory (SPI/DMTS) in collaboration with the laboratory of Prof.
Rifat Hamoudi (University of Sharjah, UAE) generated human brain organoids of both sexes. For this, they
started with induced pluripotent stem cells obtained from cells taken from male or female donors. The organoids were
selected at the optimal maturation stage to study hypoxic injuries during brain development.
Proteomic analyses conducted by
LI2D (SPI/DMTS) reveal several things:
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First, the representation of cellular markers evolves according to the maturation stage of the organoids, these markers concern, in particular, neurogenesis, astrogliogenesis, and cellular growth,
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Hypoxic stress is associated with mitochondrial dysfunction and altered energy metabolism in brain organoids of both sexes,
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Organoids "derived from women" show
increased metabolic adaptationstrong>,
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Those "derived from men" exhibit
alterations in protein quality control pathways, essential for maintaining integrity.
By identifying distinct cellular mechanisms based on sex, this study opens new perspectives for the development of predictive biomarkers and more targeted therapeutic strategies, with the ambition of improving the management of newborns exposed to oxygen deprivation.
Contact Institut des sciences du vivant Frédéric-Joliot :