Mitochondrial Dysfunction Induced by High Estradiol Concentrations in Endometrial Epithelial Cells

Area of Science:

• Reproductive biology
• Cellular and molecular biology
• Mitochondrial research

Background:

• Supraphysiological estradiol (E2) concentrations post-ovarian stimulation are linked to reduced embryo implantation rates in in vitro fertilization (IVF).
• Endometrial epithelial cell (EEC) apoptosis is observed following high E2 exposure, with mitochondria playing a critical role in this process.

Purpose of the Study:

• To investigate the impact of high estradiol (E2) concentrations on mitochondrial function in endometrial epithelial cells (EECs).

Main Methods:

• Human EECs were cultured in vitro with varying E2 concentrations (10⁻¹⁰ to 10⁻⁷ M).
• In vivo studies examined mouse EECs following equine chorionic gonadotropin (eCG) administration to simulate high E2 effects during the implantation window.
• Mitochondrial DNA content, ATP production, mitochondrial morphology, and reactive oxygen species (ROS) generation were assessed.

Main Results:

• Supraphysiological E2 significantly decreased mitochondrial DNA and ATP production in EECs, both in vitro and in vivo.
• High E2 led to reduced mitochondrial staining, fewer mitochondria, and increased ROS production.
• N-acetyl-cysteine pretreatment mitigated high E2-induced ROS, while coenzyme Q10 had no effect.

Conclusions:

• Elevated estradiol concentrations induce extramitochondrial ROS production in endometrial epithelial cells.
• This increased ROS leads to subsequent mitochondrial dysfunction, potentially impacting fertility.