Role of progesterone receptor in inguinal hernia formation via skeletal muscle fibrosis [Hernia_Xenium]

Inguinal hernia development has been linked to fibrosis and atrophy of the lower abdominal muscle (LAM). We have shown that exogenous adminstration of estradiol (E2) and progesterone (P4) in mice can induce LAM fibrosis, muscle atrophy, and hernia development in mice, and that concurrent inhibition of progesterone receptor signaling using the drug RU486 can prevent this process. Utilizing a combination of single-nuclear transcriptomics and epigenomics, we analyzed the effects of E2 and P4 on the different cell types in the LAM to determine how these compounds contribute to hernia development. Xenium spatial transcriptomics of LAM tissue of treated WT mice allowed for validation of cell type colocalization and differential gene analysis. In this study, LAM sections were harvested from WT mice after 10 weeks of treatment with vehicle, E2+P4, or E2+P4+RU486 and analyzed using Xenium spatial transcriptomics from 10X Genomics.