{Reference Type}: Journal Article
{Title}: Single-cell transcriptomic profiling unveils insights into ovarian fibrosis in obese mice.
{Author}: Xiao B;Dai Z;Li Z;Xu D;Yin H;Yang F;Sun N;
{Journal}: Biol Direct
{Volume}: 19
{Issue}: 1
{Year}: 2024 Jul 2
{Factor}: 7.173
{DOI}: 10.1186/s13062-024-00496-9
{Abstract}: <B>BACKGROUND: </B>Adiposity profoundly impacts reproductive health in both humans and animals. However, the precise subpopulations contributing to infertility under obese conditions remain elusive.<BR><B>RESULTS: </B>In this study, we established an obese mouse model through an eighteen-week high-fat diet regimen in adult female mice. Employing single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive single-cell atlas of ovarian tissues from these mice to scrutinize the impact of obesity on the ovarian microenvironment. ScRNA-seq revealed notable alterations in the microenvironment of ovarian tissues in obese mice. Granulosa cells, stromal cells, T cells, and macrophages exhibited functional imbalances compared to the control group. We observed heightened interaction strength in the SPP1-CD44 pairing within lgfbp7+ granulosa cell subtypes and Il1bhigh monocyte subtypes in the ovarian tissues of obese mice. Moreover, the interaction strength between Il1bhigh monocyte subtypes and Pdgfrb+ stromal cell subtypes in the form of TNF - TNFrsf1α interaction was also enhanced subsequently to obesity, potentially contributing to ovarian fibrosis pathogenesis.<BR><B>CONCLUSIONS: </B>We propose a model wherein granulosa cells secrete SPP1 to activate monocytes, subsequently triggering TNF-α secretion by monocytes, thereby activating stromal cells and ultimately leading to the development of ovarian fibrosis. Intervening in this process may represent a promising avenue for improving clinical outcomes in fertility treatments for obese women.