Uterine Epithelial Progesterone Receptor Governs Uterine Receptivity Through Epithelial Cell Differentiation
| Autor: | Tomoyuki Hirata, Shizu Aikawa, Tamer Taha, Mona Gebril, Ryoko Shimizu-Hirota, Yutaka Osuga, Mitsunori Matsuo, Tomoyuki Fujii, Takehiro Hiraoka, Osama Al Balah, Norihiko Takeda, Tetsuaki Kaku, Yasushi Hirota, Shun Akaeda, Yamato Fukui, Mohamed Amr. H. Elnoury |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Stromal cell media_common.quotation_subject Uterus Mice Transgenic 030209 endocrinology & metabolism Biology Extracellular matrix Andrology Endometrium Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Progesterone receptor medicine Animals Embryo Implantation skin and connective tissue diseases Ovulation Progesterone media_common Epithelial cell differentiation Cell Differentiation Embryo 030104 developmental biology medicine.anatomical_structure Female Signal transduction Receptors Progesterone hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 161 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endocr/bqaa195 |
| Popis: | Progesterone receptor (PGR) is indispensable for pregnancy in mammals. Uterine PGR responds to the heightened levels of ovarian progesterone (P4) after ovulation and regulates uterine gene transcription for successful embryo implantation. Although epithelial and stromal P4-PGR signaling may interact with each other to form appropriate endometrial milieu for uterine receptivity and the subsequent embryo attachment, it remains unclear what the specific roles of epithelial P4-PGR signaling in the adult uterus are. Here we generated mice with epithelial deletion of Pgr in the adult uterus (Pgrfl/flLtfCre/+ mice) by crossing Pgr-floxed and Ltf-Cre mice. Pgrfl/flLtfCre/+ mice are infertile due to the impairment of embryo attachment. Pgrfl/flLtfCre/+ uteri did not exhibit epithelial growth arrest, suggesting compromised uterine receptivity. Both epithelial and stromal expressions of P4-responsive genes decreased in Pgrfl/flLtfCre/+ mice during the peri-implantation period, indicating that epithelial Pgr deletion affects not only epithelial but stromal P4 responsiveness. In addition, uterine LIF, an inducer of embryo attachment, was decreased in Pgrfl/flLtfCre/+ mice. The RNA-seq analysis using luminal epithelial specimens dissected out by laser capture microdissection revealed that the signaling pathways related to extracellular matrix, cell adhesion, and cell proliferation are altered in Pgr fl/flLtf Cre/+ mice. These findings suggest that epithelial PGR controls both epithelial and stromal P4 responsiveness and epithelial cell differentiation, which provides normal uterine receptivity and subsequent embryo attachment. |
| Databáze: | OpenAIRE |
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