Integrated single-cell and spatial transcriptomics reveal microenvironment disruptions by androgen in mouse ovary

Elevated levels of androgen are risk factors for disrupted follicular maturation in the polycystic ovary syndrome (PCOS), a reproductive disease in women. As essential cell types for follicular maturation, granulosa and thecal cells respond to androgen, but their responses are unclear at the subpopulation level. Using single-cell RNA sequencing and spatial transcriptomics, we examined the subpopulation and function alterations in an androgen-induced PCOS-like mouse model. The results demonstrated that the granulosa cell subset 5 (GC5) was active in inflammation and the thecal cell subtype 2 (TC2) had an enhanced activity in lipid metabolism. The two subsets were expanded in population size and intercellular signaling pathways, such as Ptn-Ncl and Mdk-Ncl. The results reveal that androgen induced landscape and function shifts in the two cell types under the condition of impaired follicular maturation. The study characterizes the ovarian microenvironment in responses to androgen in PCOS mice.