Mass Spectrometry-Based Untargeted Metabolomics Identifies Distinct Metabolic Signatures in Infertility: A Comparative Analysis of PCOS, POR, and NOR

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dc.authorid0000-0003-4810-6771
dc.authorid0000-0003-0818-7714
dc.authorid0000-0003-1235-3957
dc.contributor.authorDemirel, Metin
dc.contributor.authorAlim, Mehtap
dc.contributor.authorKoktasoglu, Fatmanur
dc.contributor.authorAtakul, Nil
dc.contributor.authorGuner, Ebru
dc.contributor.authorAydin, Ayse Nur Isik
dc.contributor.authorKafali, Sanem Naz
dc.date.accessioned2026-01-31T15:08:15Z
dc.date.available2026-01-31T15:08:15Z
dc.date.issued2025
dc.departmentİstanbul Beykent Üniversitesi
dc.description.abstractBackgroundInfertility affects approximately 15% of reproductive-age couples, with polycystic ovary syndrome and poor ovarian reserve being major contributing factors. Metabolomic profiling of follicular fluid offers insights into the underlying metabolic disturbances associated with these infertility phenotypes. This study aims to identify metabolic biomarkers distinguishing PCOS, POR, and male factor infertility, which may facilitate improved diagnostic and therapeutic strategies.MethodsA total of 119 participants were categorized into three groups: PCOS (n = 39), POR (n = 40), and NOR (n = 40). Liquid chromatography-high-resolution mass spectrometry was used for untargeted metabolomic profiling. Metabolites were identified using HMDB, MassBank, and MoNA, while pathway analysis was performed using KEGG. Statistical analyses were conducted using R and Python, including one-way ANOVA, t-tests, and Mann-Whitney U tests, with False Discovery Rate correction applied.ResultsDistinct metabolic alterations were observed among the groups. Trehalose-6-phosphate, taurocholate, and N,N-dimethylglycine emerged as the most significantly altered metabolites, showing strong discriminatory potential between PCOS and POR. PCOS patients exhibited reduced levels of taurocholate, mycalemide, and trehalose-6-phosphate, whereas NOR patients showed elevated levels of N,N-dimethylglycine and argininosuccinate. The POR group demonstrated increased levels of 1-methyl-2-pyrrolidone and haplopine, along with a broader metabolite distribution.ConclusionThis study reveals phenotype-specific metabolic signatures in PCOS and POR, identifying taurocholate, mycalemide, and N,N-dimethylglycine as potential follicular biomarkers. These findings contribute to a deeper understanding of the metabolic basis of infertility and highlight the potential of follicular fluid metabolomics for precision medicine in reproductive health.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBITAK)
dc.description.sponsorshipOpen access funding provided by the Scientific and Technological Research Council of Turkiye (TUBITAK).
dc.identifier.doi10.1007/s43032-025-01908-5
dc.identifier.endpage2282
dc.identifier.issn1933-7191
dc.identifier.issn1933-7205
dc.identifier.issue7
dc.identifier.pmid40537734
dc.identifier.scopus2-s2.0-105008648608
dc.identifier.scopusqualityQ1
dc.identifier.startpage2270
dc.identifier.urihttps://doi.org./10.1007/s43032-025-01908-5
dc.identifier.urihttps://hdl.handle.net/20.500.12662/10636
dc.identifier.volume32
dc.identifier.wosWOS:001511717000001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer Heidelberg
dc.relation.ispartofReproductive Sciences
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260128
dc.subjectUntargeted metabolomics
dc.subjectFollicular fluid
dc.subjectMetabolic pathways
dc.subjectInfertility
dc.subjectPolycystic ovary syndrome
dc.subjectPoor ovarian reserve
dc.subjectTaurocholate
dc.subjectTrehalose-6-phosphate
dc.titleMass Spectrometry-Based Untargeted Metabolomics Identifies Distinct Metabolic Signatures in Infertility: A Comparative Analysis of PCOS, POR, and NOR
dc.typeArticle

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