Abstract
This study addresses the critical gap in understanding the ovarian lipidome's abundance, distribution, and vulnerability to environmental disruptors, a largely unexplored field. Leveraging the capabilities of matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI), we embarked on a novel exploration of the ovarian lipidome in both mouse and human healthy tissues. Our findings revealed that the obesogenic chemical tributyltin (TBT), at environmentally relevant exposures, exerts a profound and region-specific impact on the mouse ovarian lipidome. TBT exposure predominantly affects lipid species in antral follicles and oocytes, suggesting a targeted disruption of lipid homeostasis in these biologically relevant regions. Our comprehensive approach, integrating advanced lipidomic techniques and bioinformatic analyses, documented the disruptive effects of TBT, an environmental chemical, on the ovarian lipid landscape. Similar to mice, our research also unveiled distinct spatial lipidomic signatures corresponding to specific ovarian compartments in a healthy human ovary that may also be vulnerable to disruption by chemical exposures. Findings from this study not only underscore the vulnerability of the ovarian lipidome to environmental factors but also lay the groundwork for unraveling the molecular pathways underlying ovarian toxicity mediated through lipid dysregulation.