Sigma-1 receptor is involved in diminished ovarian reserve possibly by influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis

• DOI: 10.18632/aging.103166
• Publication Date: 2020-05-14T19:00:26Z
• Authors: Lile Jiang; Jinquan Cui; Cuilian Zhang; Juanke Xie; Shaodi Zhang; Dongjun Fu; Wei Duo
• Keywords: Adult; Granulosa Cells; Ovary; Apoptosis; Endoplasmic Reticulum Stress; 3. Good health; 03 medical and health sciences; Sigma-1 Receptor; 0302 clinical medicine; Humans; Receptors, sigma; Female; Ovarian Reserve; Research Paper

Sigma non-opioid intracellular receptor 1 (sigma-1 receptor), a non-opioid transmembrane protein, is located on cellular mitochondrial membranes and endoplasmic reticulum. Current research has demonstrated that sigma-1 receptor is related to human degenerative diseases. This study is focused on the effects of sigma-1 receptor on the pathophysiological process of diminished ovarian reserve (DOR) and granulosa cells (GCs) apoptosis. Sigma-1 receptor concentration in follicular fluid (FF) and serum were negatively correlated with basal follicle-stimulating hormone (FSH) and positively correlated with anti-mullerian hormone (AMH), antral follicle count (AFC). Sigma-1 receptor reduction in GCs was accompanied by endoplasmic reticulum stress (ERS)-mediated apoptosis in women with DOR. Plasmid transfection was used to establish SIGMAR1-overexpressed and SIGMAR1-knockdown human granulosa-like tumor (KGN) cell and thapsigargin (TG) was used to induce ERS KGN cells. We found that KGN cells treated with endogenous sigma-1 receptor ligand dehydroepiandrosterone (DHEA) and sigma-1 receptor agonist PRE-084 showed similar biological effects to SIGMAR1-overexpressed KGN cells and opposite effects to SIGMAR1-knockdown KGN cells. DHEA may improve DOR patients' pregnancy outcomes by upregulating sigma-1 receptor and downregulating ERS-mediated apoptotic genes in GCs. Thus, sigma-1 receptor may be a potential ovarian reserve biomarker, and ligand-mediated sigma-1 receptor activation could be a future approach for DOR therapy.