Mitochondrial Dysfunction Induced by High Estradiol Concentrations in Endometrial Epithelial Cells

Abstract

Context A supraphysiological estradiol (E2) concentration after ovarian stimulation is known to result in lower embryo implantation rates in in vitro fertilization. Endometrial epithelial cell (EEC) apoptosis occurs after the stimulation with high E2 concentrations, and mitochondria play important roles in cell apoptosis. Objective To investigate the mitochondrial function in EECs after the stimulation with high E2 concentrations. Materials and Methods Human EECs were purified and cultured with different E2 concentrations (10-10, 10–9, 10–8, 10–7 M) in vitro, in which 10–7 M is supraphysiologically high. Eight-week-old female mouse endometrium was obtained 5.5 days after the injection of 1.25 IU or 20 IU equine chorionic gonadotropin, roughly during the embryo implantation window, to examine the in vivo effects of high E2 concentrations on mouse EECs. Results In vivo and in vitro experiments demonstrated decreased mitochondrial DNA contents and ATP formation after EECs were stimulated with supraphysiologically high E2 concentrations than those stimulated with a physiologic E2 concentration. Less prominent immunofluorescence mitochondrial staining, fewer mitochondria numbers under electron microscopy, lower 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide aggregate/monomer ratio, and greater reactive oxygen species (ROS) production were found after EECs were stimulated with supraphysiologically high E2 concentrations. The high E2-induced ROS production was reduced when EECs were pretreated with N-acetyl-cysteine in vitro, but remained unchanged after the pretreatment with coenzyme Q10. Conclusion High E2 concentrations increase extramitochondrial ROS production in EECs and subsequently result in mitochondrial dysfunction.

Role of 17β-Estradiol on Cell Proliferation and Mitochondrial Fitness in Glioblastoma Cells

“…Others reported that long-term E2 treatment increased nuclear respiratory factor-1 (NRF-1) protein in cerebral blood vessels of ovariectomized rats [15]. Interestingly, high estradiol concentrations (about 10-8 M) decrease the mitochondrial DNA contents, and ATP formation and these effects were not showed at minor concentrations [16,17]. For this reason, in this work, we study the effect of estradiol at low concentrations.…”

“…We inserted the E-plate 16 into a cradle pocket of the RTCA DP analyzer, and we performed blank reading to measure the background impedance of cell culture media. We added 100 μl of a cell solution with a final concentration of 2500 cells/well in the E-plate 16 e specific PCR products were detected by the fluorescence of SYBR Green, the doublestranded DNA binding dye. Primers were designed using BLAST ® (Basic Local Alignment Search Tool, NBCI, NIH), considering the shortest amplicon proposed: primers' sequences are shown in Table 1, and β-actin was used as the housekeeping gene.…”

The Association Between Serum Estradiol Levels on hCG Trigger Day and Live Birth Rates in Non-PCOS Patients: A Retrospective Cohort Study

“…According to previous reports, when E2 levels reach a certain threshold, the adverse effects of high E2 levels on endometrial receptivity may be related to weakened endometrial blood flow ( 36 , 37 ), enhanced uterine contractility ( 38 ), interference with glycogen synthesis and secretion ( 39 ), intrauterine histopathological changes of nuclear amygdala channels ( 40 , 41 ), and changes in mitochondrial function ( 26 , 42 ). High E2 concentrations also promoted the apoptosis of endometrial gland cells in a positive feedback pathway, further damaging the receptivity of the endometrium ( 43 ).…”

Effect of Administrating Coenzyme Q10 with Clomiphene Citrate on Ovulation Induction in Polycystic Ovary Syndrome Cases with Resistance to Clomiphene Citrate: A Randomized Controlled Trial

“…High estrogen concentration is seen in women with PCOS that enhances extra mitochondrial oxidative stress in endometrial cells and leads to decreased implantation and poor pregnancy rates ( 14 ). In our study, women treated with combination had better conception rate and better endometrial thickness at the time of trigger.…”