CONTEXT: High serum estradiol (E2) concentrations result in adverse reproductive outcome in in vitro fertilization cycles, and the detrimental effects are probably due to impaired endometrial receptivity. OBJECTIVE: Endometrial glandular cells (EGCs) are the cells that embryos first interact with during implantation. Our objective is to examine the in vitro EGC alterations after high E2 treatment. DESIGN: This was a prospective study. SETTING: The study was conducted at a tertiary university hospital. PATIENTS: Six women in the follicular phase participated in the study. INTERVENTIONS: EGCs were purified from human endometrium and cultured with different concentrations (0, 10(-9), 10(-8), 10(-7), 10(-5), 10(-4) M) of E2. MAIN OUTCOME MEASURE(S): EGC apoptosis and its underlying mechanism were measured. RESULTS: In vitro BeWo spheroid-EGC implantation assay demonstrated that the stimulation with 10(-5) and 10(-4) M E2 for 2 days decreased embryo implantation potentials. Presence of apoptotic bodies and DNA fragmentation and an increased percentage of sub-G1 phase were found in EGCs treated with high E2 concentrations. The high E2-treated EGCs could be rescued from apoptosis after the addition of estrogen receptor antagonist ICI 182 780. Western blot revealed increased inhibitory-κB (IκB)-α expression and decreased nuclear factor-κB (NF-κB) expression in high E2-treated EGCs, and NF-κB binding site-driven luciferase activity was decreased as well. When EGCs were pretreated with IκB-α small interfering RNA, high E2-induced B cell lymphoma 2 (Bcl-2) down-regulation did not occur and EGCs apoptosis was reduced. Bcl-2 overexpression also rescued high E2-induced EGCs from apoptosis. CONCLUSIONS: High E2 concentrations induced EGCs apoptosis through enhancing IκB-α expression, which in turn suppressed NF-κB expression. The decreased nuclear NF-κB subsequently inhibited Bcl-2 expression and accordingly enhanced EGC apoptosis.
CONTEXT: High serum estradiol (E2) concentrations result in adverse reproductive outcome in in vitro fertilization cycles, and the detrimental effects are probably due to impaired endometrial receptivity. OBJECTIVE: Endometrial glandular cells (EGCs) are the cells that embryos first interact with during implantation. Our objective is to examine the in vitro EGC alterations after high E2 treatment. DESIGN: This was a prospective study. SETTING: The study was conducted at a tertiary university hospital. PATIENTS: Six women in the follicular phase participated in the study. INTERVENTIONS:EGCs were purified from human endometrium and cultured with different concentrations (0, 10(-9), 10(-8), 10(-7), 10(-5), 10(-4) M) of E2. MAIN OUTCOME MEASURE(S): EGC apoptosis and its underlying mechanism were measured. RESULTS: In vitro BeWo spheroid-EGC implantation assay demonstrated that the stimulation with 10(-5) and 10(-4) M E2 for 2 days decreased embryo implantation potentials. Presence of apoptotic bodies and DNA fragmentation and an increased percentage of sub-G1 phase were found in EGCs treated with high E2 concentrations. The high E2-treated EGCs could be rescued from apoptosis after the addition of estrogen receptor antagonist ICI 182 780. Western blot revealed increased inhibitory-κB (IκB)-α expression and decreased nuclear factor-κB (NF-κB) expression in high E2-treated EGCs, and NF-κB binding site-driven luciferase activity was decreased as well. When EGCs were pretreated with IκB-α small interfering RNA, high E2-induced B cell lymphoma 2 (Bcl-2) down-regulation did not occur and EGCs apoptosis was reduced. Bcl-2 overexpression also rescued high E2-induced EGCs from apoptosis. CONCLUSIONS: High E2 concentrations induced EGCs apoptosis through enhancing IκB-α expression, which in turn suppressed NF-κB expression. The decreased nuclear NF-κB subsequently inhibited Bcl-2 expression and accordingly enhanced EGC apoptosis.
Authors: Glykeria I Karatasiou; J K Bosdou; C A Venetis; L Zepiridis; K Chatzimeletiou; T B Tarlatzi; G Lainas; B C Tarlatzis; G Grimbizis; E M Kolibianakis Journal: J Assist Reprod Genet Date: 2020-05-29 Impact factor: 3.412
Authors: Krzysztof Lukaszuk; Joanna Liss; Michal Kunicki; Waldemar Kuczynski; Ewa Pastuszek; Grzegorz Jakiel; Lukasz Plociennik; Krzysztof Zielinski; Judyta Zabielska Journal: Biomed Res Int Date: 2015-04-02 Impact factor: 3.411