Abstract

Endometriosis is a common benign gynecological disease, characterized by growth and proliferation of endometrial glands and stroma outside the uterus. With studies showing metabolic changes in various biofluids of endometriosis women, we have set upon to investigate whether endometrial tissue show differences in their metabolic profiles. 1H NMR analysis was performed on eutopic endometrial tissue of women with endometriosis and controls. Analysis was performed on spectral data and on relative concentrations of metabolites obtained from spectra using multivariate and univariate data analysis. Analysis shows that various energy, ketogenic and glucogenic metabolites have significant altered concentrations in various stages of endometriosis. In addition, altered tissue metabolites in minimal and mild stages of endometriosis were explored in serum of these patients to assess their role in disease diagnosis. For Stage I diagnosis alanine was found to have 90% sensitivity (true positives) and 58% specificity (true negatives). For Stage II diagnosis alanine, leucine, lysine, proline and phenylalanine showed significant altered levels in serum. While sensitivity of these serum metabolites varied between 69.2–100% the specificity values ranged between 58.3–91.7%. Further, a regression model generated with this panel of serum markers showed an improved sensitivity and specificity of 100% and 83%, respectively for Stage II diagnosis.

Highlights

  • Endometriosis is an estrogen dependent benign gynecological disorder and is defined by the presence of endometrial tissue consisting of glands and stroma outside the uterine cavity; commonly on the pelvic peritoneum, ovaries, and rectovaginal septum

  • The present study investigates 1H nuclear magnetic resonance (NMR) based metabolic profiling of endometrial tissue to obtain a comprehensive idea of the metabolic perturbations associated with disease development and progression

  • Several metabolites from diverse chemical classes could be identified from the 1H NMR spectra of endometrial tissue samples

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Summary

Introduction

Endometriosis is an estrogen dependent benign gynecological disorder and is defined by the presence of endometrial tissue consisting of glands and stroma outside the uterine cavity; commonly on the pelvic peritoneum, ovaries, and rectovaginal septum. Extra pelvic sites such as thorax[1], cutaneous tissues[2], bone[3], and even the brain[4] are found to have infiltrating endometrial tissue growth It is one of the most common causes of female infertility of unknown etiology which affects menstruating women in their reproductive age and may result from imbalance of the cellular equilibrium[5]. Metabolomics is increasingly being recognized as a powerful tool for elucidating pathogenesis and disease biomarker identification This new ‘omics’ approach is used to perform global analysis of low molecular weight metabolites in various biological samples. NMR and MS based metabolomics studies on endometrial fluid[13], follicular fluid[14], urine[10], serum[15] and plasma[16] of endometriosis women have shown remarkable changes in their metabolite profile. The levels of altered tissue metabolites were further investigated in serum of paired endometriosis patients for their role in mild stage of the disease diagnosis

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