Metabolomic profiling and biochemical evaluation of the follicular fluid of endometriosis patients

Abstract

Diseases are complex systems that can be studied through the integration of data derived from different disciplines to obtain a global and reliable picture of the biological phenomenon under investigation. Based on the recent observations that the metabolomics profiling of follicular fluids reflects the ovarian microenvironment of women and that endometriosis represents an example of complex diseases, clearly diagnosed by laparoscopy, we thought that the follicular fluids of endometriosis patients can represent a study model to evaluate the possibility of integrating data obtained by different approaches. Hence, the aim of this work was to analyze and integrate different clinical chemistry parameters with specific reference to the metabolic profile, inflammatory state and cell damage by a H-NMR approach and biochemical analysis in the follicular fluids of women with different stages of endometriosis (I-II and III-IV) subjected to the In Vitro Fertilization (IVF) cycle. Our analysis evidenced that in the follicular fluids of endometriosis patients the levels of phospholipids, lactate, insulin, PTX3, CXCL8, CXCL10, CCL11 and VEGF were higher whereas those of some fatty acids, lysine, choline, glucose, aspartate, alanine, leucine, valine, proline, phosphocholine, total LDH as well its LDH-3 isoform were lower in comparison to the control group. The levels of LDHB, PTX3 and insulin receptor were also confirmed by RT-PCR applied on cumulus cells surrounding oocytes retrieved from the patients. The reduced oocyte quality observed in patients with endometriosis can be certainly correlated to the different levels of these molecules. These data represent how the integration of different experimental approaches may be useful for understanding the underlying mechanisms of a complex disease and can lead to a better clinical management of endometriosis.

Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages

“…Metabolites not only represent the final products of biological regulatory processes but also act as communicators between the information-rich genome and the functional phenotype. In the past few years, several studies identified a list of potential diagnostic candidates in peritoneal fluid, blood and urine from endometriosis patients at different stages of disease and menstrual cycle [ 9 , 10 ]. However, potential biomarkers from the eutopic endometrium remain unknown.…”

Ovarian endometrioma infiltrating neutrophils orchestrate immunosuppressive microenvironment

“…Other chemokines such as CXCL1, CXCL2, CXCL3, and G-CSF can also attract neutrophils [28]. Consistently, patients with endometriosis displayed a significant higher production of CXCL1, CXCL2, and CXCL8 in the peritoneal fluid as compared to those from controls [29][30][31]. Secretion of CXCL8 is significantly higher in the eutopic endometrial stromal cells from women with endometriosis than that in the control [32].…”

Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos but Not Their Quality

“…Endometriosis could also affect the metabolic processes, thereby altering the microenvironment of the follicle and the oocyte development. Indeed, metabolomic signatures related to endometriosis have been identified in the follicular fluid [36][37][38], and in other biological fluids [39,40], despite some reports suggesting the opposite [41]. One study reported that the follicular fluid of infertile women with endometriosis could impair nuclear maturation and promote meiotic anomalies in bovine oocytes matured in vitro [42].…”