scholarly journals FKBP51 regulates decidualization through Ser473 dephosphorylation of AKT

Reproduction ◽  
2018 ◽  
Vol 155 (3) ◽  
pp. 283-295 ◽  
Author(s):  
Muyun Wei ◽  
Ying Gao ◽  
Bingru Lu ◽  
Yulian Jiao ◽  
Xiaowen Liu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Binding Protein ◽  
Follicular Phase ◽  
Hormone Response ◽  
Rt Pcr ◽  
Endometrial Stromal Cells ◽  
Fk 506 ◽  
Forkhead Box ◽  
Pathological Conditions

Defective decidualization of human endometrial stromal cells (ESCs) has recently been highlighted as an underlying cause of implantation failure. FK-506-binding protein 51 (FKBP51) has been shown to participate in the steroid hormone response and the protein kinase B (AKT) regulation process, both of which are important pathways involved in decidualization. The objective of the present study was to investigate the potential effects and mechanisms of FKBP51 in the regulation of ESC decidualization. By performing immunohistochemical staining on an endometrial tissue microarray (TMA) derived from normal females, we found that FKBP51 expression was much higher in the luteal phase than in the follicular phase in ESCs. Primary ESCs were isolated from patients to build an in vitro decidualization model through co-culture with medroxyprogesterone acetate (MPA) and 8-bromoadenosine (cAMP). SC79, a specific AKT activator in various physiological and pathological conditions, and shRNA-FKBP51 were used to examine the roles of AKT and FKBP51 in decidualization. The Western blot and RT-PCR results showed that FKBP51, insulin-like growth factor-binding protein 1 (IGFBP1) and prolactin (PRL) expression increased in ESCs treated with MPA + cAMP; meanwhile, the level of p-Ser473 AKT (p-S473 AKT) decreased and forkhead box protein O1 (FOXO1A) expression increased. Decidualization was inhibited by the AKT activator SC79 and the transfection of FKBP51-shRNA by affecting protein synthesis, cell morphology, cell growth and cell cycle. Furthermore, this inhibition was rescued by FKBP51-cDNA transfection. The results supported that FKBP51 promotes decidualization by reducing the Ser473 phosphorylation levels in AKT.

scholarly journals Dysregulation of In Vitro Decidualization of Human Endometrial Stromal Cells by Insulin via Transcriptional Inhibition of Forkhead Box Protein O1

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0171004 ◽  
Author(s):  
Dorina Ujvari ◽  
Ivika Jakson ◽  
Shabnam Babayeva ◽  
Daniel Salamon ◽  
Bence Rethi ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Endometrial Stromal Cells ◽  
Transcriptional Inhibition ◽  
Forkhead Box

scholarly journals Resveratrol enhances decidualization of human endometrial stromal cells

Reproduction ◽  
2020 ◽  
Vol 159 (4) ◽  
pp. 453-463 ◽  
Author(s):  
Ana Cecilia Mestre Citrinovitz ◽  
Laila Langer ◽  
Thomas Strowitzki ◽  
Ariane Germeyer
Keyword(s):  
Cell Cycle ◽  
Stromal Cells ◽  
Antioxidant Properties ◽  
Trophoblast Invasion ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Rt Pcr ◽  
Endometrial Stromal Cells

The differentiation of endometrial stromal cells (ESC), named decidualization, is essential to regulate trophoblast invasion and to support pregnancy establishment and progression. Decidualization follows ESC proliferation and it has been described that cell cycle arrest contributes to a proper decidualization. Interestingly, resveratrol, a natural compound derived from grapes with antioxidant properties, has been widely studied in relation to endometrial health. However, little is known about the effect of resveratrol supplementation during decidualization. Therefore, in this study we evaluate the effect of resveratrol supplementation during decidualization. We used primary and immortalized human ESC and we decidualized them in vitro with a decidualization cocktail containing medroxyprogesterone acetate, estradiol and 8-Bromo-cyclic AMP. Pre-decidualized cells were further treated with the decidualization cocktail supplemented with resveratrol. Our results show that resveratrol supplementation increased, in a dose-dependent manner, the expression levels of prolactin and IGFBP1 (RT-PCR and ELISA), indicating an enhanced in vitro decidualization of human ESC. This enhanced decidualization was accompanied by a decrease in cell proliferation (crystal violet and CellTiter proliferation assay) and by changes in the mRNA levels of key cell cycle regulators (RT-PCR). Furthermore, resveratrol supplementation seemed to enhance decidualization by reinforcing the effect of the decidualization cocktail. We believe that resveratrol could to be an effective supplementation to reinforce hormone action during human ESC decidualization and that further insights into resveratrol action and its interaction with estradiol and progesterone signaling pathways could facilitate the identification of new therapeutic strategies for the improvement of women’s health.

scholarly journals Expression and the Biological Activities of Insulin-Like Growth Factor-Binding Protein Related Protein 1 in Rat Uterus during the Periimplantation Period

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5243-5251 ◽  
Author(s):  
Kazuhiro Tamura ◽  
Takahiko Hara ◽  
Masahiko Kutsukake ◽  
Ken Iwatsuki ◽  
Mayuko Yanagida ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Binding Protein ◽  
Biological Activities ◽  
Related Protein ◽  
Rat Uterus ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract IGF binding protein-related protein 1 (IGFBP-rP1) is highly expressed in the rat uterus around the time of implantation. In the present study, we determined the periimplantation localization of IGFBP-rP1 mRNA and assessed the effects of recombinant IGFBP-rP1 on the proliferative and prostacyclin (PGI2)-producing abilities of cultured endometrial cells early in pregnancy. IGFBP-rP1 mRNA was detected at high levels in endometrial stromal cells close to the smooth muscle of interimplantation sites around the time of implantation but absent from decidual zones surrounding the embryo. Differential uterine IGFBP-rP1 expression was also recognized in the delayed implanting pregnant model, but the level of mRNA decreased as decidual tissues formed in the decidualization model. Recombinant IGFBP-rP1 inhibited the proliferation of endometrial stromal cells in vitro and arrested them in the G1 phase of the cell cycle. Furthermore, IGFBP-rP1 significantly stimulated PGI2 synthesis and cyclooxygenase II mRNA expression in myometrial cells, both of which are essential molecules for successful implantation. These data suggest that IGFBP-rP1 is an implantation-associated protein and that it modulates the proliferation of rat uterine cells and their production of PGI2 during the periimplantation period.

scholarly journals Endometrial regeneration with endometrial epithelium: homologous orchestration with endometrial stroma as a feeder

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryo Yokomizo ◽  
Yukiko Fujiki ◽  
Harue Kishigami ◽  
Hiroshi Kishi ◽  
Tohru Kiyono ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Stromal Cells ◽  
Therapeutic Option ◽  
Three Dimensional ◽  
Fertility Treatment ◽  
Feeder Cells ◽  
Endometrial Stromal Cells ◽  
Thin Endometrium ◽  
Endometrial Epithelial Cells

Abstract Background Thin endometrium adversely affects reproductive success rates with fertility treatment. Autologous transplantation of exogenously prepared endometrium can be a promising therapeutic option for thin endometrium; however, endometrial epithelial cells have limited expansion potential, which needs to be overcome in order to make regenerative medicine a therapeutic strategy for refractory thin endometrium. Here, we aimed to perform long-term culture of endometrial epithelial cells in vitro. Methods We prepared primary human endometrial epithelial cells and endometrial stromal cells and investigated whether endometrial stromal cells and human embryonic stem cell-derived feeder cells could support proliferation of endometrial epithelial cells. We also investigated whether three-dimensional culture can be achieved using thawed endometrial epithelial cells and endometrial stromal cells. Results Co-cultivation with the feeder cells dramatically increased the proliferation rate of the endometrial epithelial cells. We serially passaged the endometrial epithelial cells on mouse embryonic fibroblasts up to passage 6 for 4 months. Among the human-derived feeder cells, endometrial stromal cells exhibited the best feeder activity for proliferation of the endometrial epithelial cells. We continued to propagate the endometrial epithelial cells on endometrial stromal cells up to passage 5 for 81 days. Furthermore, endometrial epithelium and stroma, after the freeze-thaw procedure and sequential culture, were able to establish an endometrial three-dimensional model. Conclusions We herein established a model of in vitro cultured endometrium as a potential therapeutic option for refractory thin endometrium. The three-dimensional culture model with endometrial epithelial and stromal cell orchestration via cytokines, membrane-bound molecules, extracellular matrices, and gap junction will provide a new framework for exploring the mechanisms underlying the phenomenon of implantation. Additionally, modified embryo culture, so-called “in vitro implantation”, will be possible therapeutic approaches in fertility treatment.

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