Single-cell sequencing reveals alterations in the ovarian immune microenvironment regulated by 17β-estradiol in neonatal mice

The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate, and the neonatal ovarian immune microenvironment, particularly its modulation by estrogen, has not been comprehensively characterized. In this study, the effects of 17β-estradiol (E₂), a key regulator of immune function, were investigated using single-cell transcriptomic profiling of C57BL/6J neonatal mouse ovaries after E₂ treatment. Results revealed dynamic alterations in the proportion of immune cell types after E₂ treatment, accompanied by changes in cytokine and chemokine expression. Detailed analyses of gene expression, cell states, and developmental trajectories across distinct cell types indicated that E₂ treatment influenced cell differentiation and development. Notably, E₂ treatment reduced the abundance of macrophages and promoted a phenotypic transition from M1 to M2 macrophages. These findings demonstrate that the neonatal mouse ovarian immune microenvironment is sensitive to estrogenic modulation, which governs both the distribution and functional specialization of resident immune cells, offering novel mechanistic insights into the immunomodulatory roles of estrogen across various immune cell types.