Neurotoxicity and Reproductive Hormone Dysregulation: Oxidative Stress and Immunomodulatory Mechanisms Across the Gut-Brain-Gonadal Axis
Nakawungu Catherine
Department of Pharmaceutical Microbiology and Biotechnology Kampala International University Uganda
Email: catherine.nakawungu@studwc.kiu.ac.ug
ABSTRACT
The gut–brain–gonadal (GBG) axis represents a complex bidirectional network integrating endocrine, neural, and immune signals to regulate homeostasis. Emerging evidence indicates that dysregulation of reproductive hormones, such as estrogens, progesterone, and androgens, intersects with oxidative stress and immune signaling to exacerbate neurotoxicity. Disturbances in the gut microbiota, altered hypothalamic–pituitary–gonadal (HPG) axis activity, and chronic systemic inflammation converge to disrupt neuronal survival, synaptic plasticity, and neuroendocrine balance. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) promote DNA damage, mitochondrial dysfunction, and lipid peroxidation, while immune mediators including cytokines, Toll-like receptors, and microglial activation amplify neuroinflammatory cascades. Hormonal fluctuations-particularly hypoestrogenism, androgen deficiency, and altered gonadotropin secretion-further modulate oxidative and immune pathways, heightening susceptibility to neurodegeneration, mood disorders, and reproductive dysfunction. This review synthesizes mechanistic insights into the interplay of oxidative stress and immunomodulation within the GBG axis, highlighting their roles in neurotoxicity and endocrine disruption. It also discusses therapeutic implications, including microbiota-targeted strategies, antioxidants, and immunomodulatory agents that may restore axis homeostasis and mitigate disease progression.
Keywords: neurotoxicity, reproductive hormones, oxidative stress, immunomodulation, gut-brain-gonadal axis
CITE AS: Nakawungu Catherine (2025). Neurotoxicity and Reproductive Hormone Dysregulation: Oxidative Stress and Immunomodulatory Mechanisms Across the Gut-Brain-Gonadal Axis. IDOSR JOURNAL OF APPLIED SCIENCES 10(2):23-28, 2025. https://doi.org/10.59298/IDOSRJAS/2025/102.2328