Plasma metabolomic characterization of premature ovarian insufficiency

Abstract

Background Premature ovarian insufficiency (POI) patients are predisposed to metabolic disturbances, including in lipid metabolism and glucose metabolism, and metabolic disorders appear to be a prerequisite of the typical long-term complications of POI, such as cardiovascular diseases or osteoporosis. However, the metabolic changes underlying the development of POI and its subsequent complications are incompletely understood, and there are few studies characterizing the disturbed metabolome in POI patients. The aim of this study was to characterize the plasma metabolome in POI by using ultrahigh-performance liquid chromatography–mass spectrometry (UHPLC–MS/MS) metabolomics and to evaluate whether these disturbances identified in the plasma metabolome relate to ovarian reserve and have diagnostic value in POI. Methods This observational study recruited 30 POI patients and 30 age- and body mass index (BMI)-matched controls in the Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, from January 2018 to October 2020. Fasting venous blood was collected at 9:00 am on days 2–4 of the menstrual cycle and centrifuged for analysis. An untargeted quantitative metabolomic analysis was performed using UHPLC–MS/MS. Results Our study identified 48 upregulated and 21 downregulated positive metabolites, and 13 upregulated and 48 downregulated negative metabolites in the plasma of POI patients. The differentially regulated metabolites were involved in pathways such as caffeine metabolism and ubiquinone and other terpenoid-quinone biosynthesis. Six metabolites with an AUC value > 0.8, including arachidonoyl amide, 3-hydroxy-3-methylbutanoic acid, dihexyl nonanedioate, 18-HETE, cystine, and PG (16:0/18:1), were correlated with ovarian reserve and thus have the potential to be diagnostic biomarkers of POI. Conclusion This UHPLC–MS/MS untargeted metabolomics study revealed differentially expressed metabolites in the plasma of patients with POI. The differential metabolites may not only be involved in the aetiology of POI but also contribute to its major complications. These findings offer a panoramic view of the plasma metabolite changes caused by POI, which may provide useful diagnostic and therapeutic clues for POI disease.

Metabolomic Analysis Reveals Association between Decreased Ovarian Reserve and In Vitro Fertilization Outcomes

“…Glycerophospholipids serve as the primary constituents of mammalian cell membranes, exerting a pivotal role in signal transduction, cellular proliferation, protein function, and other essential biological processes [ 57 , 67 , 68 ]. In line with these previous studies, we also observed an up-regulation of the glycerophospholipid metabolic pathway in women with DOR.…”

Application of an Exhausted Fermentation Broth Obtained from Biohydrogen Production in an Apple Orchard: Assessment of Fruit Quality

“…The most abundant metabolites detected by LC-SACI-MS, following the fermentation process, were organic acids; in particular, formic acid (89.5 g L −1 ), butyric acid (7.45 g L −1 ) and butanedioic acid (3.58 g L −1 ). Organic acids are typical metabolites in dark fermentation processes as described by different authors [21,22]. Clostridium spp.…”

Lipid and glucose metabolism in senescence

“…Premature ovarian insufficiency (POI) is the condition of ovarian function decline leading to amenorrhea for over a year before 40 years of age ( 237 ), which may be associated with genetic, medical, immunological, environmental, and other factors. POI is associated with metabolic disturbances, including glucose and lipid metabolism, which may increase the risk of long-term complications, such as cardiovascular diseases and osteoporosis ( 238 ). Glucose metabolism is regulated by insulin.…”

“…Estrogen also affects lipid metabolism by regulating the expression and activity of enzymes and receptors involved in lipid synthesis, transport, and degradation ( 240 ). Zhou et al ( 238 ) found that patients with POI had higher levels of plasma glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, a marker of insulin resistance), plasma triglycerides, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B compared with healthy controls. Moreover, they identified several metabolites related to glucose metabolism and lipid metabolism that were altered in patients with POI, including lactate, pyruvate, citrate, carnitine, acylcarnitine, glycerol, and glycerophospholipids.…”