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Integrated Eutopic Endometrium and Non-Depleted Serum Quantitative Proteomic Analysis Identifies Candidate Serological Markers of Endometriosis

Manousopoulou A, Hamdan M, Fotopoulos M, Garay-Baquero DJ, Teng J, Garbis SD, et al.

Proteomics Clin Appl, 2019 05;13(3):e1800153.
PMID: 30488576 DOI: 10.1002/prca.201800153

BACKGROUND: Endometriosis affects about 4% of women in the reproductive age and is associated with subfertility. The aim of the present study is to examine the integrated quantitative proteomic profile of eutopic endometrium and serum from women with endometriosis compared to controls in order to identify candidate disease-specific serological markers.
METHODS: Eutopic endometrium and serum from patients with endometriosis (n = 8 for tissue and n = 4 for serum) are, respectively, compared to endometrium and serum from females without endometriosis (n = 8 for tissue and n = 4 for serum) using a shotgun quantitative proteomics method. All study participants are at the proliferative phase of their menstrual cycle.
RESULTS: At the tissue and serum level, 1214 and 404 proteins are differentially expressed (DEPs) in eutopic endometrium and serum, respectively, of women with endometriosis versus controls. Gene ontology analysis shows that terms related to immune response/inflammation, cell adhesion/migration, and blood coagulation are significantly enriched in the DEPs of eutopic endometrium, as well as serum. Twenty-one DEPs have the same trend of differential expression in both matrices and can be further examined as potential disease- and tissue-specific serological markers of endometriosis.
CONCLUSIONS: The present integrated proteomic profiling of eutopic endometrium and serum from women with endometriosis identify promising serological markers that can be further validated in larger cohorts for the minimally invasive diagnosis of endometriosis.

Matched MeSH terms: Endometriosis/metabolism*
Endometriosis and infertility: raised iron concentration in the peritoneal fluid and its effect on the acrosome reaction

Arumugam K

Hum Reprod, 1994 Jun;9(6):1153-7.
PMID: 7962392

Endometriosis and infertility are commonly associated. This study investigated the role of accelerated lipid peroxidation of spermatozoa by the peritoneal fluid of patients with endometriosis as a cause for this association. It proposes that the increased iron concentration present in the fluid of these patients acts as a catalyst for the process. Peritoneal fluid from 25 patients with endometriosis and 25 matched controls was obtained at laparoscopy. Spermatozoa were incubated in the fluid from both groups and the subsequent acrosome reaction rates analysed. The relationship between these results and iron concentration in the fluid was examined. A significant decrease in the acrosome reaction rate was seen in the endometriotic group (P = 0.034). Overall, a decrease in the acrosome reaction rate was associated with an increased iron concentration in the fluid (18 of the 25 pairs). In mild disease, (six of 11 pairs), the relationship was not as marked as that in severe disease (12 of 14 pairs). These results suggest that the peritoneal fluid in patients with endometriosis has a detrimental action on the acrosome reaction of spermatozoa in vitro.

Matched MeSH terms: Endometriosis/metabolism*
De novo formation of adhesions in endometriosis: the role of iron and free radical reactions

Arumugam K, Yip YC

Fertil Steril, 1995 Jul;64(1):62-4.
PMID: 7789581

OBJECTIVE: To show that raised iron levels in the peritoneal fluid (PF) of patients with endometriosis catalyze free radical reactions that results in the tissue destruction and fibrosis seen in these patients.
DESIGN: A case-controlled study of the iron levels (microgram/mL) in the pelvic PF of 12 patients with moderate-to-severe disease, 15 patients with minimal-to-mild disease and in 17 women with normal pelvises were compared. As an index of free radical reactions through lipid peroxidation, the levels of malondialdehyde levels (ng/mL) were assessed simultaneously in the same specimens.
RESULTS: Controlling for the phase of the menstrual cycle, significantly higher levels of iron were seen in patients with endometriosis, the levels being correlated with the severity of the disease. However no such corresponding relationship was seen in the malondialdehyde levels in the PF.
CONCLUSIONS: These results suggest that raised iron levels in the PF do not play a role in catalyzing free radical reactions as judged by the degree of lipid peroxidation.

Matched MeSH terms: Endometriosis/metabolism*
Endometriosis and infertility: the role of exogenous lipid peroxides in the peritoneal fluid

Arumugam K, Dip YC

Fertil Steril, 1995 Jan;63(1):198-9.
PMID: 7805914

OBJECTIVE: To determine if lipid peroxides were raised in the pelvic peritoneal fluid of patients with endometriosis.
DESIGN: Control study involving patients with and without endometriosis.
METHODS: The lipid peroxide (malondialdehyde) levels in the pelvic PF of 12 patients with moderate-to severe endometriosis, 15 patients with minimal-mild endometriosis and 13 patients with normal pelvises were compared.
RESULTS: The level of lipid peroxides were not affected by the presence nor the severity of endometriosis.
CONCLUSION: Accelerated lipid peroxidation does not appear to play a role in the causal relationship between endometriosis and infertility.

Matched MeSH terms: Endometriosis/metabolism*
Fulltext The sensitivity of the DNA damage checkpoint prevents oocyte maturation in endometriosis

Hamdan M, Jones KT, Cheong Y, Lane SI

Sci Rep, 2016 11 14;6:36994.
PMID: 27841311 DOI: 10.1038/srep36994

Mouse oocytes respond to DNA damage by arresting in meiosis I through activity of the Spindle Assembly Checkpoint (SAC) and DNA Damage Response (DDR) pathways. It is currently not known if DNA damage is the primary trigger for arrest, or if the pathway is sensitive to levels of DNA damage experienced physiologically. Here, using follicular fluid from patients with the disease endometriosis, which affects 10% of women and is associated with reduced fertility, we find raised levels of Reactive Oxygen Species (ROS), which generate DNA damage and turn on the DDR-SAC pathway. Only follicular fluid from patients with endometriosis, and not controls, produced ROS and damaged DNA in the oocyte. This activated ATM kinase, leading to SAC mediated metaphase I arrest. Completion of meiosis I could be restored by ROS scavengers, showing this is the primary trigger for arrest and offering a novel clinical therapeutic treatment. This study establishes a clinical relevance to the DDR induced SAC in oocytes. It helps explain how oocytes respond to a highly prevalent human disease and the reduced fertility associated with endometriosis.

Matched MeSH terms: Endometriosis/metabolism