Endometrial breakdown with sustained progesterone release involves NF-κB-mediated functional progesterone withdrawal in a mouse implant model
Autor: | Jing-shan Zhao, Li-Jing Cui, Ai-ying Li, Yu Liu, Guo-Hong Zhang, Bin He, Jian-Ping Zhang, Li Chu, Yunfeng Li, Xiangbo Xu, Jie-Dong Wang |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty 030219 obstetrics & reproductive medicine Stromal cell Decidualization NF-κB Cell Biology Biology Endometrium 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Endocrinology chemistry In vivo Internal medicine Progesterone receptor Genetics medicine Implant Receptor Developmental Biology |
Zdroj: | Molecular Reproduction and Development. 83:780-791 |
ISSN: | 1040-452X |
Popis: | Irregular uterine bleeding is a major side effect of long-acting progestogen-only contraceptives in women, and is the primary reason women discontinue their use. In this study, a mouse model of endometrial breakdown was established using a subcutaneous progesterone implant to understand how irregular bleeding begins. Although progestogens sustained decidualization, endometrial breakdown was still observed in this model. We, therefore, hypothesized that endometrial breakdown might involve functional progesterone withdrawal. Using co-immunoprecipitation assays, we observed the constitutive activation of nuclear factor kappa-b (NF-κB) p65 and its interaction with the progesterone receptor (PGR); moreover, transcriptional activity of the PGR was also repressed by NF-κB activity in primary mouse and human decidual stromal cells that mimic progesterone maintenance. Yet the ratio of PGR-B to PGR-A was not increased in the mouse model. In vivo comparison of endometrial breakdown induced by progesterone withdrawal to that seen during sustained progesterone exposure, in the presence of NF-κB inhibitors, revealed that NF-κB-mediated functional progesterone withdrawal is involved in endometrial breakdown in this implant model. These data prompt further studies to determine the homology of this functional progesterone withdrawal mechanism in human endometrium. Mol. Reprod. Dev. 83: 780-791, 2016 © 2016 Wiley Periodicals, Inc. |
Databáze: | OpenAIRE |
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