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- Title
IHH, SHH, and primary cilia mediate epithelial-stromal cross-talk during decidualization in mice.
- Authors
Li, Bo; Yan, Ya-Ping; He, Yu-Ying; Liang, Chen; Li, Meng-Yuan; Wang, Ying; Yang, Zeng-Ming
- Abstract
The establishment of pregnancy depends on interactions between the epithelial and stromal cells of the endometrium that drive the decidual reaction that remodels the stroma and enables embryo implantation. Decidualization in mice also depends on ovarian hormones and the presence of a blastocyst. Hedgehog signaling is transduced by primary cilia in many tissues and is involved in epithelial-stromal cross-talk during decidualization. We found that primary cilia on mouse uterine stromal cells increased in number and length during early pregnancy and were required for decidualization. In vitro and in vivo, progesterone promoted stromal ciliogenesis and the production of Indian hedgehog (IHH) in the epithelium and Sonic hedgehog (SHH) in the stroma. Blastocyst-derived TNF-α also induced epithelial IHH, which stimulated the production of SHH in the stroma through a mechanism that may involve the release of arachidonic acid from epithelial cells. In the stroma, SHH activated canonical Hedgehog signaling through primary cilia and promoted decidualization through a mechanism that depended on interleukin-11 (IL-11) and primary cilia. Our findings identify a primary cilia–dependent network that controls endometrial decidualization and suggest primary cilia as a candidate therapeutic target for endometrial diseases. Hedgehogs remodel the uterus for pregnancy: Interactions between uterine epithelial and stromal cells trigger decidualization, the remodeling of the stroma necessary for embryo implantation. Decidualization in mice also depends on the presence of a blastocyst and requires the Hedgehog family member IHH. Li et al. demonstrated that decidualization required primary cilia, which increased in the mouse uterine stroma prior to implantation. In mice and isolated mouse uterine cells, progesterone or blastocysts stimulated the epithelial cells to produce IHH, which in turn induced SHH in the stroma. Stromal SHH acted as an autocrine signal and stimulated decidualization in manner that depended on primary cilia and the decidualization factor IL-11. These findings identify distinct roles for different Hedgehog family members in decidualization and highlight the importance of primary cilia in the endometrial remodeling that is required for pregnancy and that is dysregulated in diseases such as endometriosis. —AMV
- Subjects
ENDOMETRIUM; CILIA &; ciliary motion; EMBRYO implantation; HEDGEHOG signaling proteins; ENDOMETRIAL diseases; EPITHELIAL cells; STROMAL cells
- Publication
Science Signaling, 2023, Vol 16, Issue 774, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.add0645