Dynamic Expression of Interleukin-33 and ST2 in the Mouse Reproductive Tract Is Influenced by Superovulation

Abstract

Interleukin-33 (IL-33) is an IL-1 family cytokine with pleiotropic effects on diverse cell types. Dysregulated IL-33 signaling has been implicated in pregnancy-related disorders, including preeclampsia and recurrent pregnancy loss, and in ovarian function in women undergoing controlled ovarian stimulation for in vitro fertilization. To date, expression of IL-33 and its receptor subunit, ST2, in the female reproductive tract remains poorly characterized. We identify IL-33-expressing oocytes surrounded by ST2-expressing granulosa cells at all stages of follicular development, in addition to IL-33+ and ST2+ non-endothelial cells in the ovarian stroma and theca layer in ovaries from adult mice. These expression patterns are similar in estrus- and diestrus-stage adults and in pubescent mice, suggesting a role for IL-33 signaling in ovarian function throughout development and in the estrous cycle. In the uterus, we find expression of IL-33 and ST2 in glandular and luminal epithelia during estrus and at the initiation of pregnancy. Uterine IL-33 expression was modulated by the estrous cycle and was reduced in pubescent females. Last, superovulation increases transcripts for IL-33 and the soluble form of ST2 (sST2) in ovaries, and for IL-33 in uteri. Collectively, our findings lay the foundation for studies identifying cell type-specific requirements for IL-33/ST2 signaling in the establishment and maintenance of mouse pregnancy.