snRNA-seq of human ovaries reveals heat shock proteins are associated with obesity related cancer risk

Obesity significantly impacts female reproductive health and increases the risk of gynecological tumors. However, the specific transcriptional changes that occur in the ovarian microenvironment during obesity-induced stress and the relationship between obesity and ovarian cancer remain unclear. Our study investigated the single-cell landscape of the ovarian cortex in individuals with varying BMI levels by snRNA-seq, revealing weight-stage related cellular composition deviations and expression profile irregularities. Results: Using single-cell high-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA), we identified distinct obesity-related gene modules within various subpopulations of stroma cells and blood vascular endothelial cells. Notably, we observed a negative correlation between BMI and heat shock protein (HSP) family genes. Specifically, we found that HSPD1 might function as a potential regulator of ovarian carcinogenesis and progression under conditions of obesity, as supported by our co-analysis with data from three bulk RNA-seq ovarian cancer databases. Our findings suggested that lower expression of HSPD1 indicated a poorer prognosis for ovarian cancer. Our study identified a cluster of genes in ovarian cells that are suppressed by obesity, including those belonging to HSP family genes. These findings provide valuable insights for investigating the link between obesity and ovarian diseases.