Correlation of Glycolysis-immune-related Genes in the Follicular Microenvironment of Endometriosis Patients with ART Outcomes

Reprod Sci. 2024 Apr 1. doi: 10.1007/s43032-024-01518-7. Online ahead of print.

Abstract

Endometriosis (EMT) -related infertility has been a challenge for clinical research. Many studies have confirmed that abnormal alterations in the immune microenvironment and glycolysis are instrumental in causing EMT-related infertility. Recently, our research team identified several key glycolysis-immune-related genes in the endometrial cells of EMT patients. This study aimed to further investigate the expression patterns of pyruvate dehydrogenase kinase 3 (PDK3), glypican-3 (GPC3), and alcohol dehydrogenase 6 (ADH6), which are related to glycolysis and immunity, in the follicular microenvironment of infertile patients with EMT using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assays. According to the results, compared to the patients with tubal factor infertility, the concentrations of PDK3 and GPC3 were considerably increased in the follicular environment of EMT patients, while ADH6 expression was significantly reduced. The number of oocytes retrieved, the transferable embryo rate, and the cumulative clinical pregnancy rate of EMT patients were significantly reduced, and there was a correlation with the level of PDK3, GPC3, and ADH6 in Follicular Fluid (FF). The area under the receiver operating characteristic (ROC) curve for predicting clinical pregnancy in infertile patients with EMT for PDK3, GPC3, ADH6, and their combination was 0.732, 0.705, 0.855, and 0.879, respectively (P < 0.05). In conclusion, our research indicates that glycolysis-immune-related genes may contribute to infertility in EMT patients through immune infiltration, and disruption of mitochondrial and oocyte functions. The combined detection of PDK3, GPC3, and ADH6 in FF helps to predict clinical pregnancy outcomes in infertile patients with EMT.

Keywords: Assisted reproductive technology; Endometriosis; Glycolysis; Immune microenvironment; Infertility.