Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in vivo and in vitro. We confirmed that PM2.5 induced adverse gestational outcomes such as increased fetal mortality rates, decreased fetal numbers and weight, damaged placental structure, and increased apoptosis of trophoblasts. Additionally, PM2.5 induced dysfunction of the trophoblast cell line HTR8/SVneo, including in its proliferation, apoptosis, invasion, migration and angiogenesis. Moreover, we comprehensively analyzed the transcriptional landscape of HTR8/SVneo cells exposed to PM2.5 through RNA-Seq and observed that PM2.5 triggered overexpression of pathways involved in oxidative stress and mitochondrial apoptosis to damage HTR8/SVneo cell biological functions through CYP1A1. Mechanistically, PM2.5 stimulated KLF9, a transcription factor identified as binding to CYP1A1 promoter region, which further modulated the CYP1A1-driven downstream phenotypes. Together, this study demonstrated that the KLF9/CYP1A1 axis played a crucial role in the toxic progression of PM2.5 induced adverse pregnancy outcomes, suggesting adverse effects of environmental pollution on pregnant females and putative targeted therapeutic strategies.

• Gestational GenX exposure causes fetal growth restriction and placental damage. • GenX induces offspring vascular maldevelopment and endothelial dysfunction. • GenX triggers endothelial ferroptosis via GSH/SOD depletion & MDA/Fe²⁺/ROS rise. • GenX binds GPX4, promoting its ubiquitination-mediated degradation. • GPX4 overexpression rescues GenX-induced ferroptosis & endothelial damage.

Gestational diabetes mellitus (GDM) is frequently linked to placental overgrowth and hypertrophy, while maternal hyperglycaemic environment consistently in

Wilms' tumor (WT) and rhabdoid tumor (RT) are the predominant renal neoplasms in pediatric patients, and their metastatic potential significantly impacts the prognosis of affected children. However, limited research has been conducted on elucidating the underlying molecular mechanisms driving metastasis in these tumors, resulting in a dearth of well-defined molecular targets. Based on the clinical staging information available in the TARGET database for WT and RT, we investigated the differential gene expression profiles and associated molecular pathways implicated in metastasis. Interestingly, our analysis revealed that WT and RT tumor metastases shared a highly expressed gene IMPA2, which was associated with poor prognosis. Additionally, experimental validation confirmed that IMPA2 exerted regulatory effects on the Wnt signaling pathway as well as N-cadherin and E-cadherin levels, thereby influencing the migratory and invasive capabilities of G401 cells. Moreover, gene profiles and molecular pathways associated with IMPA2 expression were comprehensively analyzed, transcription factors potentially regulating IMPA2 were identified, and correlations with immune-related genes were determined. Regarding therapy, we identified small molecule drugs that affected IMPA2 expression and utilized molecular docking to predict their direct binding to the IMPA2 protein. These findings have provided biomarkers and therapeutic targets for the metastatic WT and RT, while the investigated targeted drugs hold promise as novel therapeutic strategies to enhance the prognosis of affected children.