Proteomics Analysis of Human Amniotic Fluid

Cho, Chan Kyung J.; Shan, Shannon J.; Winsor, Elizabeth J.T.; Diamandis, Eleftherios P.

doi:10.1074/mcp.m700090-mcp200

Cited by 159 publications

(131 citation statements)

References 24 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…During pregnancy, to further the development of fetal respiratory and digestive systems, the fetus recirculates amniotic fluid (up to 500 ml/day) via oronasal ingestion (73)(74)(75)(76). Amniotic fluid consists of maternal plasma and fetal urine, depending upon gestational stage (77)(78)(79). It is possible that blood-borne prions are trafficked with maternal plasma to amniotic fluid or that infectious prions are transported across the maternal-fetal interface via trophoblast cells from the uterine environment.…”

Section: Discussionmentioning

confidence: 99%

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

Nalls

McNulty

Hoover

et al. 2017

J Virol

View full text Add to dashboard Cite

Ample evidence exists for the presence of infectious agents at the maternal-fetal interface, often with grave outcomes to the developing fetus (i.e., Zika virus, brucella, cytomegalovirus, and toxoplasma). While less studied, pregnancyrelated transmissible spongiform encephalopathies (TSEs) have been implicated in several species, including humans. Our previous work has shown that prions can be transferred from mother to offspring, resulting in the development of clinical TSE disease in offspring born to muntjac dams infected with chronic wasting disease (CWD) (1). We further demonstrated protein misfolding cyclic amplification (PMCA)-competent prions within the female reproductive tract and in fetal tissues harvested from CWD experimentally and naturally exposed cervids (1, 2). To assess whether the PMCA-competent prions residing at the maternal-fetal interface were infectious and to determine if the real-time quaking-induced conversion (RT-QuIC) methodology may enhance our ability to detect amyloid fibrils within the pregnancy microenvironment, we employed a mouse bioassay and RT-QuIC. In this study, we have demonstrated RT-QuIC seeding activity in uterus, placentome, ovary, and amniotic fluid but not in allantoic fluids harvested from CWD-infected Reeves' muntjac dams showing clinical signs of infection (clinically CWD-infected) and in some placentomes from pre-clinically CWD-infected dams. Prion infectivity was confirmed within the uterus, amniotic fluid, and the placentome, the semipermeable interface that sustains the developing fetus, of CWD-infected dams. This is the first report of prion infectivity within the cervid pregnancy microenvironment, revealing a source of fetal CWD exposure prior to the birthing process, maternal grooming, or encounters with contaminated environments.IMPORTANCE The facile dissemination of chronic wasting disease within captive and free-range cervid populations has led to questions regarding the transmission dynamics of this disease. Direct contact with infected animals and indirect contact with infectious prions in bodily fluids and contaminated environments are suspected to explain the majority of this transmission. A third mode of transmission, from mother to offspring, may be underappreciated. The presence of pregnancyrelated prion infectivity within the uterus, amniotic fluid, and the placental structure reveals that the developing fetus is exposed to a source of prions long before exposure to the infectious agent during and after the birthing process or via contact with contaminated environments. These findings have impact on our current concept of CWD disease transmission.KEYWORDS CWD, maternal, pregnancy, prions T ransmissible spongiform encephalopathies (TSEs), or prion diseases, are proteinaceous infectious neurodegenerative diseases affecting animals, including humans (3, 4). The disease is caused by the accumulation of an aberrant misfolded form

show abstract

Section: Discussionmentioning

confidence: 99%

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

Nalls

McNulty

Hoover

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…The 2-DE gel pattern of high abundance proteins in the IS-depleted PDR sample was similar to that in the corresponding non-IS-depleted PDR sample, which suggests that high abundance proteins account for most protein in vitreous humor. In addition, the "sponge effect" may have removed low abundance proteins of interest with the 12 most abundant proteins in the IS column [33,34]. Therefore, we decided to use a relatively mild depletion method to prepare the depleted PDR vitreous sample, i.e., to deplete the PDR sample for nano-LC-MALDI-MS/MS, we used a Calbiochem kit to remove only the two most abundant proteins, i.e., albumin and IgG.…”

Section: Vitreous Protein Identification Using Nano-lc-maldi-ms/msmentioning

confidence: 99%

Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients

Kim

et al. 2007

Proteomics

133

View full text Add to dashboard Cite

Diabetes can lead to serious microvascular complications like proliferative diabetic retinopathy (PDR), which is the leading cause of blindness in adults. The proteomic changes that occur during PDR cannot be measured in the human retina for ethical reasons, but could be reflected by proteomic changes in vitreous humor. Thus, we considered that comparisons between the proteome profiles of the vitreous humors of PDR and nondiabetic controls could lead to the discovery of novel pathogenic proteins and clinical biomarkers. In this study, the authors used several proteomic methods to comprehensively examine vitreous humor proteomes of PDR patients and nondiabetic controls. These methods included immunoaffinity subtraction (IS)/2-DE/ MALDI-MS, nano-LC-MALDI-MS/MS, and nano-LC-ESI-MS/MS. The identified proteins were subjected to the Trans-Proteomic Pipeline validation process. Resultantly, 531 proteins were identified, i.e., 415 and 346 proteins were identified in PDR and nondiabetic control vitreous humor samples, respectively, and of these 531 proteins, 240 were identified for the first time in this study. The PDR vitreous proteome was also found to contain many proteins possibly involved in the pathogenesis of PDR. The proteins described provide the most comprehensive proteome listing in the vitreous humor samples of PDR and nondiabetic control patients.

show abstract

“…Mass spectrometry has been widely used to identify the proteome of fluids (13)(14)(15)(16), and specifically Gortzak-Uzan et al (17) have recently attempted to identify the proteome of ascites, both cellular and fluid fractions. As biomarkers may be present at low concentrations, (18) and ascites, like serum, contains many high abundance proteins (with a protein concentration range spanning at least 9 orders of magnitude (19)), extensive sample fractionation is necessary if biomarkers are to be found successfully using mass spectrometry.…”

mentioning

confidence: 99%

Mining the Ovarian Cancer Ascites Proteome for Potential Ovarian Cancer Biomarkers

Kuk

Kulasingam

Gunawardana

et al. 2009

Molecular & Cellular Proteomics

Self Cite

114

111

View full text Add to dashboard Cite

Current ovarian cancer biomarkers are inadequate because of their relatively low diagnostic sensitivity and specificity. There is a need to discover and validate novel ovarian cancer biomarkers that are suitable for early diagnosis, monitoring, and prediction of therapeutic response. We performed an in-depth proteomics analysis of ovarian cancer ascites fluid. Size exclusion chromatography and ultrafiltration were used to remove high abundance proteins with molecular mass >30 kDa. After trypsin digestion, the subproteome (<30 kDa) of ascites fluid was determined by two-dimensional liquid chromatography-tandem mass spectrometry. Filtering criteria were used to select potential ovarian cancer biomarker candidates. By combining data from different size exclusion and ultrafiltration fractionation protocols, we identified 445 proteins from the soluble ascites fraction using a two-dimensional linear ion trap mass spectrometer. Among these were 25 proteins previously identified as ovarian cancer biomarkers. After applying a set of filtering criteria to reduce the number of potential biomarker candidates, we identified 52 proteins for which further clinical validation is warranted. Our proteomics approach for discovering novel ovarian cancer biomarkers appears to be highly efficient because it was able to identify 25 known biomarkers and 52 new candidate biomarkers that warrant further validation. Molecular & Cellular Proteomics 8:661-669, 2009.Accounting for ϳ3% of all new cancer cases in 2008 (1) with a 1 in 59 (1.7%) lifetime probability of developing the disease, ovarian cancer is the most lethal gynecological malignancy deeming 5-6% of all cancer deaths (1). Hidden deep within the pelvis, ovarian cancer is relatively asymptomatic in early stages, and because of the lack of adequate screening, ovarian cancer has resulted in the majority of cases being presented with late stage disease in association with a low 5-year survival rate of 25-40%. When presented at an early stage, the 5-year survival rate exceeds 90% and most patients are cured by surgery alone (2). Although the most widely used serum marker for ovarian cancer is carbohydrate antigen 125 (CA125), 1 its utility as a screening marker is limited because of its high false positive rates and elevation in other malignancies such as uterine, fallopian, colon, and gastric cancer (3, 4) as well as in non-malignant conditions such as pregnancy and endometriosis (5). These reasons alone demonstrate the need and immediate benefit in using biomarkers with increased sensitivity and specificity for early diagnosis, prognosis, or monitoring of ovarian cancer.Many advanced stage ovarian cancer patients exhibit rapid growth of intraperitoneal tumors along with abdominal distention as a result of accumulation of ascites fluid in the peritoneal cavity. Mechanistically ascites formation occurs as malignant cells secrete proteins, growth factors, and cytokines that cause neovascularization, angiogenesis, increased fluid filtration, and/or lymphatic obstruction (6 -8) resulting...

show abstract

Proteomics Analysis of Human Amniotic Fluid

Cited by 159 publications

References 24 publications

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients

Mining the Ovarian Cancer Ascites Proteome for Potential Ovarian Cancer Biomarkers

Contact Info

Product

Resources

About