Application of NMR-based metabolomics to the study of endometriosis and infertility in French women

Endometriosis is a chronic inflammatory disease defined as the presence and the abnormal development of estrogen-dependent endometrial tissue outside the uterine cavity. This disease affects about 10% of women of reproductive age and more than 30% of women with infertility. Symptoms include nonspecific pelvic pain such as dysmenorrhea, dyspareunia or even severe pelvic pain although it can be asymptomatic. Despite its high prevalence and its impact on quality of life and sexual function, the pathophysiology of this disease is poorly known and its diagnosis remains very late and complicated. Thus, the discovery of early biomarkers that could help clinicians in their diagnostic process is essential. Therefore, we decided to explore this pathology by a metabolomics approach based on 1H Nuclear Magnetic Resonance (NMR) spectroscopy.
A clinical cohort of 137 French women was recruited and blood samples were collected. This cohort could be separated into four groups: two groups of women with deep endometriosis (ovarian or not) and two groups of women without endometriosis (healthy fertile women and infertility not caused by the disease). All samples were analyzed by NMR after protein removal by ultrafiltration. The generated metabolomics data were analyzed, after quantification of more than 50 metabolites, by classical multivariate and univariate analyses.
Preliminary results showed that women with deep endometriosis were discriminated from other groups. Several metabolites, i.e. acetone, 2-hydroxybutyrate, lactate, phenylalanine and urea, constituting a specific metabolic signature, were highlighted (p-value <0.05 after FDR correction) as putative biomarkers of the pathology. These metabolites were also linked to certain biological pathways that could be useful to better understand the etiology of this disease. Obviously, these results need to be confirmed in a new cohort but they pave the way for new tools for the diagnosis of endometriosis.