Iron plays an essential role in various physiological processes. A disruption in iron homeostasis can lead to severe consequences, including impaired neurodevelopment, neurodegenerative disorders, stroke, and cancer. Interestingly, the link between mental health disorders and iron homeostasis has not received significant attention. Therefore, our understanding of iron metabolism in the context of psychological diseases is incomplete. In this review, we aim to discuss the pathologies and potential mechanisms that relate to iron homeostasis in associated mental disorders. We propose the hypothesis that maintaining brain iron homeostasis can support neuronal physiological functions by impacting key enzymatic activities during neurotransmission, redox balance, and myelination. In conclusion, our review highlights the importance of investigating the relationship between trace element nutrition and the pathological process of mental disorders, focusing on iron. This nutritional perspective can offer valuable insights for the clinical treatment of mental disorders.

Controlled ovarian hyperstimulation (COH) is a cornerstone of assisted reproductive technologies, yet its effects on endometrial function and embryo implantation remain poorly understood, particularly regarding the role of hypoxia-inducible factor 2α (HIF-2α) signaling. Therefore, the objective of this study was to investigate whether COH-induced endometrial dysfunction impairs mouse embryo implantation through the HIF-2α pathway. A COH mouse model was established using gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) administration. Embryo implantation status was evaluated on gestational days 5, 6, and 20; endometrial tissues were analyzed for HIF-2α pathway activity via immunohistochemistry (IHC), immunofluorescence (IF), Western blot (WB) and quantitative real-time PCR (qRT-PCR); histological changes were assessed by Jones silver staining and transmission electron microscopy (TEM); serum estradiol (E₂), progesterone (P₄), and prolactin (PRL) levels were measured by radioimmunoassay (RIA). COH mice exhibited reduced total embryo implantation rates (on day 5, 6 and 20), together with decreased serum E₂, P₄, and PRL levels. COH mice exhibited preserved luminal epithelium integrity with increased microvillus density and continuous basement membrane structure. qRT-PCR and WB demonstrated significantly downregulated HIF-2α expression at both mRNA and protein levels, accompanied by reduced downstream RAB27B (member of RAS oncogene family)/matrix metalloproteinase 9 (MMP9) and lysyl oxidase (LOX)/adrenomedullin (ADM) signaling, which associated with impaired luminal epithelium detachment and compromised trophoblast invasion. Together, these findings identify HIF-2α as a potential key mediator of COH-induced endometrial microenvironment alterations, revealing molecular mechanisms underlying implantation failure. Importantly, the HIF-2α-RAB27B/MMP9 and HIF-2α-LOX/ADM axes are highlighted as promising therapeutic targets to optimize assisted reproductive outcomes.

Fear memory, vital for environmental adaptation, depends on enhanced synaptic plasticity in the prefrontal cortex and hippocampus. Our prior study linked brain iron deficiency to impaired contextual fear memory, though mechanisms remained unclear. Here we show that brain iron levels and endothelial ferroportin 1 (FPN1) expression rise during fear memory formation. Using endothelial Cadherin (Cdh5) mediated Fpn1 knockout mice (Fpn1^Cdh5-CKO), we demonstrated that endothelial Fpn1 deficiency leads to brain iron deficiency, which reduces synaptic plasticity and impairs contextual fear memory. Transcriptomics analysis identified lipocalin 2 (LCN2) as a potential target linking endothelial FPN1 to synaptic plasticity. Intracerebroventricular injection of nanoliposome-encapsulated Lcn2 shRNA further confirmed the LCN2-matrix metalloproteinase 9 (MMP9) axis mediates brain-derived neurotrophic factor precursor (pro-BDNF) cleavage, thereby suppressing BDNF-tropomyosin receptor kinase B signaling and impairing plasticity and memory. Our findings suggest the LCN2-MMP9 functional axis may link iron transport in blood-brain barrier to fear memory, offering prospective therapeutic targets for iron-related disorders like post-traumatic stress disorder.