Department of Reproductive Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Department of Health Services Administration, Temple University College of Public Health, Philadelphia, PA, 19122, USA.
Reprod Sci. 2024 Nov;31(11):3357-3367. doi: 10.1007/s43032-024-01518-7. Epub 2024 Apr 1.
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.
子宫内膜异位症(EMT)相关的不孕一直是临床研究的难题。许多研究证实,免疫微环境和糖酵解的异常改变在引起 EMT 相关不孕中起着重要作用。最近,我们的研究团队在 EMT 患者的子宫内膜细胞中鉴定出了几个关键的糖酵解-免疫相关基因。本研究旨在进一步探讨丙酮酸脱氢酶激酶 3(PDK3)、聚糖蛋白 3(GPC3)和醇脱氢酶 6(ADH6)在 EMT 不孕患者卵泡微环境中的表达模式,采用酶联免疫吸附试验(ELISA)和实时荧光定量聚合酶链反应(qRT-PCR)检测。结果表明,与输卵管因素不孕患者相比,EMT 患者卵泡环境中 PDK3 和 GPC3 的浓度明显升高,而 ADH6 的表达显著降低。EMT 患者获卵数、可移植胚胎率和累积临床妊娠率均明显降低,且与卵泡液(FF)中 PDK3、GPC3 和 ADH6 的水平相关。PDK3、GPC3、ADH6 及其组合预测 EMT 不孕患者临床妊娠的受试者工作特征(ROC)曲线下面积分别为 0.732、0.705、0.855 和 0.879(P<0.05)。综上所述,本研究表明糖酵解-免疫相关基因可能通过免疫浸润和破坏线粒体和卵子功能导致 EMT 患者不孕。FF 中 PDK3、GPC3 和 ADH6 的联合检测有助于预测 EMT 不孕患者的临床妊娠结局。