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

An ongoing controversy persists regarding the ovarian immunomodulating function of estrogen. A comprehensive characterization of the immune microenvironment within neonatal ovaries, particularly its modulation by estrogen, remains insufficiently explored. In this study, we examined the influence of 17β-estradiol (E2), a pivotal regulator of immune microenvironment, on immune cells in neonatal ovaries by analyzing single-cell transcriptome data of C57BL/6J mice from control (CTRL) and E2 groups. Results elucidated the dynamic alternations in the proportion of immune cell types after E2 treatment, accompanied by changes in cytokines and chemokines expression. Concretely, we analyzed the alternations associated with genes expression, cell states and cell fates in various cell types after E2 treatment, which further revealed the roles in cell development and differentiation. Moreover, the number of macrophages was decreased and E2 treatment led to the transformation of M1 macrophages into M2 macrophages. Collectively, these findings indicate that the ovarian immune microenvironment is intricately associated with estrogen levels; this likely regulates both the quantity and functional diversity of resident immune cells, thereby offering novel insights into the immunomodulatory roles of estrogen across various immune cell types.