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Review
. 2025 May 24;15(1):67.
doi: 10.1186/s13578-025-01402-0.

Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids

Romane Gaston-Breton  1 , Clémence Disdier  1 , Henrik Hagberg  2 , Aloïse Mabondzo  3
Affiliations
Review

Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids

Romane Gaston-Breton et al. Cell Biosci. .

Abstract

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental morbidities in full-term infants. There is strong evidence of sexual differences in hypoxic-ischemic (HI) injury where male neonates are at higher risk as they are subject to more pronounced neurological deficits and death than females. The cellular and molecular mechanisms underlying these sexual discrepancies in HI injury are poorly understood. Mitochondrial dysregulation has been increasingly explored in brain diseases and represents a major target during HI events. In this review, we discuss (1) different mitochondrial functions in the central nervous system (2), mitochondrial dysregulation in the context of HI injury (3), sex-dependent mitochondrial pathways in HIE and (4) modeling of mitochondrial dysfunction using human brain organoids. Gaining insight into these novel aspects of mitochondrial function will offer valuable understanding of brain development and neurological disorders such as HI injury, paving the way for the discovery and creation of new treatment approaches.

Keywords: Brain organoid; Hypoxic-ischemic encephalopathy; Mitochondria; Sexual differences.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: The authors declare that the manuscript does not contain any individual person’s data in any form (including any individual details, images or videos). Competing interests: The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Mitochondrial dysregulation during HI events. Mitochondria play a crucial role in HI, injury with production of ROS species, apoptosis, increased membrane permeability, lipid peroxidation, autophagy, protein oxidation and disruption of calcium homeostasis. Created using BioRender.com and SMART Servier Medical Art
Fig. 2
Fig. 2
Sex differences in mitochondria signaling pathways in the context of HI injury. Evidence of sex differences in mitochondrial dysfunction regarding oxidative damage, autophagy, protein oxidation and apoptosis pathways. Inspired by [122] and created using BioRender.com and SMART Servier Medical Art
See this image and copyright information in PMC

References

    1. Yıldız EP, Ekici B, Tatlı B. Neonatal hypoxic ischemic encephalopathy: an update on disease pathogenesis and treatment. Expert Rev Neurother. 2017;17(5):449–59. - PubMed
    1. Long M, Brandon DH. Induced hypothermia for neonates with hypoxic-ischemic encephalopathy. J Obstet Gynecol Neonatal Nurs. 2007;36(3):293–8. - PubMed
    1. Allen KA, Brandon DH. Hypoxic ischemic encephalopathy: pathophysiology and experimental treatments. Newborn Infant Nurs Rev. 2011;11(3):125–33. - PMC - PubMed
    1. Lawn JE, Cousens S, Zupan J. 4 Million neonatal deaths: when? Where? Why? Lancet. 2005;365(9462):891–900. - PubMed
    1. Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2005;90(5):F380–7. - PMC - PubMed

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