The Current Applications of Metabolomics in Understanding Endometriosis: A Systematic Review

Overview

Journal Metabolites

Publisher MDPI

Date 2025 Jan 24

PMID 39852392

Authors

Blake Collie

Jacopo Troisi

Martina Lombardi

Steven Symes

Sean Richards

Affiliations

Soon will be listed here.

Abstract

Endometriosis is a common gynecological disease that affects approximately 10-15% of reproductive-aged women worldwide. This debilitating disease has a negative impact on the quality of life of those affected. Despite this condition being very common, the pathogenesis is not well understood. Metabolomics is the study of the array of low-weight metabolites in a given sample. This emerging field of omics-based science has proved to be effective at furthering the understanding of endometriosis. In this systematic review, we seek to provide an overview of the application of metabolomics in endometriosis. We highlight the use of metabolomics in locating biomarkers for identification, understanding treatment mechanisms and symptoms, and relating external factors to endometriosis. The literature search took place in the Web of Science, Pubmed, and Google Scholar based on the keywords "metabolomics" AND "endometriosis" or "metabolome" AND "endometriosis". We found 58 articles from 2012 to 2024 that met our search criteria. Significant alterations of lipids, amino acids, as well as other compounds were present in human and animal models. Discrepancies among studies of significantly altered metabolites make it difficult to make general conclusions on the metabolic signature of endometriosis. However, several individual metabolites were elevated in multiple studies of women with endometriosis; these include 3-hydroxybutyrate, lactate, phosphatidic acids, succinate, pyruvate, tetradecenoylcarnitine, hypoxanthine, and xanthine. Accordingly, L-isoleucine and citrate were reduced in multiple studies of women with endometriosis. Including larger cohorts, standardizing testing methods, and studying the individual phenotypes of endometriosis may lead to more separable results.

References

Li J, Guan L, Zhang H, Gao Y, Sun J, Gong X . Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages. Reprod Biol Endocrinol. 2018; 16(1):42. PMC: 5928574. DOI: 10.1186/s12958-018-0360-z. View

Ni Z, Sun S, Bi Y, Ding J, Cheng W, Yu J . Correlation of fecal metabolomics and gut microbiota in mice with endometriosis. Am J Reprod Immunol. 2020; 84(6):e13307. DOI: 10.1111/aji.13307. View

Bouet P, Chao de la Barca J, El Hachem H, Descamps P, Legendre G, Reynier P . Metabolomics shows no impairment of the microenvironment of the cumulus-oocyte complex in women with isolated endometriosis. Reprod Biomed Online. 2019; 39(6):885-892. DOI: 10.1016/j.rbmo.2019.08.001. View

Wei Y, Zhang Z, Zhang Y, Li J, Ruan X, Wan Q . Nontargeted metabolomics analysis of follicular fluid in patients with endometriosis provides a new direction for the study of oocyte quality. MedComm (2020). 2023; 4(3):e302. PMC: 10229744. DOI: 10.1002/mco2.302. View

Guo H, Zhu Q, Gao H, Lyu Q, Chai W, Wu L . Metabolomics analysis of follicular fluid in ovarian endometriosis women receiving progestin-primed ovary stimulation protocol for in vitro fertilization. Sci Rep. 2023; 13(1):5747. PMC: 10082198. DOI: 10.1038/s41598-023-32797-w. View

Jana S, Dutta M, Joshi M, Srivastava S, Chakravarty B, Chaudhury K . 1H NMR based targeted metabolite profiling for understanding the complex relationship connecting oxidative stress with endometriosis. Biomed Res Int. 2013; 2013:329058. PMC: 3747613. DOI: 10.1155/2013/329058. View

Kennedy S, Bergqvist A, Chapron C, DHooghe T, Dunselman G, Greb R . ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005; 20(10):2698-704. DOI: 10.1093/humrep/dei135. View

Loy S, Zhou J, Cui L, Tan T, Ee T, Chern B . Discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum. Reprod Biomed Online. 2021; 43(4):727-737. DOI: 10.1016/j.rbmo.2021.07.002. View

Tripodi F, Castoldi A, Nicastro R, Reghellin V, Lombardi L, Airoldi C . Methionine supplementation stimulates mitochondrial respiration. Biochim Biophys Acta Mol Cell Res. 2018; 1865(12):1901-1913. DOI: 10.1016/j.bbamcr.2018.09.007. View

10.

Sun Z, Song J, Zhang X, Wang A, Guo Y, Yang Y . Novel SWATH technology for follicular fluid metabolomics in patients with endometriosis. Pharmazie. 2018; 73(6):318-323. DOI: 10.1691/ph.2018.7193. View

11.

Warowicka A, Qasem B, Dera-Szymanowska A, Wolun-Cholewa M, Florczak P, Horst N . Effect of Protoberberine-Rich Fraction of L. on Endometriosis Regression. Pharmaceutics. 2021; 13(7). PMC: 8309065. DOI: 10.3390/pharmaceutics13070931. View

12.

Cordeiro F, Cataldi T, Perkel K, do Vale Teixeira da Costa L, Rochetti R, Stevanato J . Lipidomics analysis of follicular fluid by ESI-MS reveals potential biomarkers for ovarian endometriosis. J Assist Reprod Genet. 2015; 32(12):1817-25. PMC: 4681741. DOI: 10.1007/s10815-015-0592-1. View

13.

Neuditschko B, Leibetseder M, Brunmair J, Hagn G, Skos L, Gerner M . Epithelial Cell Line Derived from Endometriotic Lesion Mimics Macrophage Nervous Mechanism of Pain Generation on Proteome and Metabolome Levels. Biomolecules. 2021; 11(8). PMC: 8393596. DOI: 10.3390/biom11081230. View

14.

Guo S . Recurrence of endometriosis and its control. Hum Reprod Update. 2009; 15(4):441-61. DOI: 10.1093/humupd/dmp007. View

15.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. PMC: 2707599. DOI: 10.1371/journal.pmed.1000097. View

16.

Vicente-Munoz S, Morcillo I, Puchades-Carrasco L, Paya V, Pellicer A, Pineda-Lucena A . Nuclear magnetic resonance metabolomic profiling of urine provides a noninvasive alternative to the identification of biomarkers associated with endometriosis. Fertil Steril. 2015; 104(5):1202-9. DOI: 10.1016/j.fertnstert.2015.07.1149. View

17.

Karaer A, Tuncay G, Mumcu A, Dogan B . Metabolomics analysis of follicular fluid in women with ovarian endometriosis undergoing in vitro fertilization. Syst Biol Reprod Med. 2018; 65(1):39-47. DOI: 10.1080/19396368.2018.1478469. View

18.

Kiesel L, Sourouni M . Diagnosis of endometriosis in the 21st century. Climacteric. 2019; 22(3):296-302. DOI: 10.1080/13697137.2019.1578743. View

19.

Szyplowska M, Tarkowski R, Kulak K . The impact of endometriosis on depressive and anxiety symptoms and quality of life: a systematic review. Front Public Health. 2023; 11:1230303. PMC: 10512020. DOI: 10.3389/fpubh.2023.1230303. View

20.

Dutta M, Anitha M, Smith P, Chiaro C, Maan M, Chaudhury K . Metabolomics Reveals Altered Lipid Metabolism in a Mouse Model of Endometriosis. J Proteome Res. 2016; 15(8):2626-33. DOI: 10.1021/acs.jproteome.6b00197. View