Urine, peritoneal fluid and omental fat proteomes of reproductive age women: Endometriosis-related changes and associations with endocrine disrupting chemicals

Abstract

Endometriosis, ectopic growth of the uterine lining (endometrium), which affects 6–11% of reproductive age women, is associated with pelvic pain and infertility. We investigated the peritoneal fluid (PF), urine and omental fat (OF) proteomes of women with endometriosis vs. individuals with no surgically visualized endometriosis. All participants were enrolled in the NICHD-funded ENDO Study. A two-step proteomic study was performed. The first, a broad survey, employed a semi-quantitative gel LC-mass spectrometry (MS) workflow: SDS PAGE fractionation, trypsin digestion and LC–MS/MS. The results showed sample integrity but failed to detect any differences between women with and without endometriosis. The second step was a quantitative analysis of OF samples. We employed another sample set (n = 30) from women ± disease and isobaric mass-tag (iTRAQ) chemistry to label peptides and 2D LC–MS/MS for protein identification and quantification. Three proteins—matrix metalloproteinase-9, neutrophil elastase, and FAM49B—were significantly lower in abundance in samples from women with endometriosis. Interestingly, neutrophil elastase and FAM49B levels were associated with higher levels of a subset of endocrine disrupting chemicals (EDCs) that were previously measured in the same samples. The results of these experiments showed the feasibility of associating endometriosis with changes in the OF protein repertoire and EDC levels. Biological significance Endometriosis, pathological growth of the uterine lining, is associated with significant morbidities, including pain and infertility. However, the causes of this common condition are poorly understood. This study determined whether endometriosis was associated with changes in the protein composition of peritoneal fluid, urine and/or omental fat. A protein of unknown function (FAM49B) and two proteinases (metalloproteinase-9, neutrophil elastase) were down regulated in OF samples from women with versus without endometriosis. These findings suggested proteinase imbalances at sites that were distant from the endometriotic lesions. Additionally, FAM49B and neutrophil elastase levels were associated with higher levels of a subset of environmental chemicals that were quantified in the same samples, suggesting other possible associations. Thus, this work generated hypotheses that will be tested in further studies.

Acupuncture as a multifunctional neuroprotective therapy ameliorates cognitive impairment in a rat model of vascular dementia: A quantitative iTRAQ proteomics study

“…Western blot analyses were performed to validate the proteomics results . The protein samples were separated by 10% SDS‐PAGE gels and transferred to PVDF membranes.…”

Modifiable life style factors and risk for incident endometriosis

“…Previous research has shown that endometriosis is prevalent after menarche and dramatically drops after menopause, which has led researchers to believe that the disorder is estrogen and progesterone dependent . Risk factors known to be associated with endometriosis include age, family history, educational attainment, age at menarche, and exposure to endocrine‐disrupting chemicals . Life style factors such as alcohol/caffeine intake, smoking, and physical activity influence oestrogen levels in the body and, therefore, may impact development of endometriosis.…”

Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models

“…For example, chronic inflammation associated with obesity and diseases such as HIV are known to increase the size and immune cell content of the omentum [111, 112]. Compared to disease-free women, Williams et al [113] observed alterations in omental proteinase expression of women with endometriosis, which correlated with increased body burden of several EDCs (although TCDD was not examined). As shown in Figure 3, compared to control animals, F1 and F3 mice exhibit a marked accumulation of immune cells within the omentum, supporting our hypothesis that these animals have a heightened “baseline” inflammatory phenotype.…”