Uterine-specific Ezh2 deletion enhances stromal cell senescence and impairs placentation, resulting in pregnancy loss.
| Autor: | Sirohi VK; Department of Physiological Sciences, University of Florida, Gainesville, FL, USA., Medrano TI; Department of Physiological Sciences, University of Florida, Gainesville, FL, USA., Kannan A; Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Bagchi IC; Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Cooke PS; Department of Physiological Sciences, University of Florida, Gainesville, FL, USA. |
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| Jazyk: | angličtina |
| Zdroj: | IScience [iScience] 2023 Jun 08; Vol. 26 (7), pp. 107028. Date of Electronic Publication: 2023 Jun 08 (Print Publication: 2023). |
| DOI: | 10.1016/j.isci.2023.107028 |
| Abstrakt: | Maternal uterine remodeling facilitates embryo implantation, stromal cell decidualization and placentation, and perturbation of these processes may cause pregnancy loss. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that epigenetically represses gene transcription; loss of uterine EZH2 affects endometrial physiology and induces infertility. We utilized a uterine Ezh2 conditional knockout (cKO) mouse to determine EZH2's role in pregnancy progression. Despite normal fertilization and implantation, embryo resorption occurred mid-gestation in Ezh2 cKO mice, accompanied by compromised decidualization and placentation. Western blot analysis revealed Ezh2 -deficient stromal cells have reduced amounts of the histone methylation mark H3K27me3, causing upregulation of senescence markers p21 and p16 and indicating that enhanced stromal cell senescence likely impairs decidualization. Placentas from Ezh2 cKO dams on gestation day (GD) 12 show architectural defects, including mislocalization of spongiotrophoblasts and reduced vascularization. In summary, uterine Ezh2 loss impairs decidualization, increases decidual senescence, and alters trophoblast differentiation, leading to pregnancy loss. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).) |
| Databáze: | MEDLINE |
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