Abstract:Proteomic analysis of AF can distinguish PE from CHTN and CTR. The discriminatory proteins were identified as proapolipoprotein A-I and SBBI42.
“…It is unlikely that the accumulation of APOA1 in the PE placenta is due to high levels of APOA1 in the maternal plasma since plasma levels APOA1 are not increased in PE [26, 27]. In a recent proteomics study of amniotic fluid, accumulation of pro-APOA1 was shown in the amniotic fluid in PE [28]. Hence, amniotic fluid may be a possible source of the accumulated APOA1 seen in the PE placenta.…”
The human placenta is a difficult tissue to work with using proteomic technology since it contains large amounts of lipids and glycogen. Both lipids and glycogen are known to interfere with the first step in the two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), the isoelectric focusing. In order to gain the best possible protein separation on 2D-PAGE, an optimized sample preparation protocol for placental proteins was developed. Two different buffers, urea/CHAPS and Hepes, were used for solubilization in combination with six different precipitation methods. The removal of glycogen from the samples by centrifugation was crucial for the final proteome maps. Solubilization with urea/CHAPS in combination with dichloromethane/methanol or acidified acetone proved to be the best precipitation procedures. When applied to clinical placenta samples apolipoprotein A1 was found to be accumulated in the preeclamptic placenta, where it may either have a nutritional effect or act as a modifier of signal transduction.
“…It is unlikely that the accumulation of APOA1 in the PE placenta is due to high levels of APOA1 in the maternal plasma since plasma levels APOA1 are not increased in PE [26, 27]. In a recent proteomics study of amniotic fluid, accumulation of pro-APOA1 was shown in the amniotic fluid in PE [28]. Hence, amniotic fluid may be a possible source of the accumulated APOA1 seen in the PE placenta.…”
The human placenta is a difficult tissue to work with using proteomic technology since it contains large amounts of lipids and glycogen. Both lipids and glycogen are known to interfere with the first step in the two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), the isoelectric focusing. In order to gain the best possible protein separation on 2D-PAGE, an optimized sample preparation protocol for placental proteins was developed. Two different buffers, urea/CHAPS and Hepes, were used for solubilization in combination with six different precipitation methods. The removal of glycogen from the samples by centrifugation was crucial for the final proteome maps. Solubilization with urea/CHAPS in combination with dichloromethane/methanol or acidified acetone proved to be the best precipitation procedures. When applied to clinical placenta samples apolipoprotein A1 was found to be accumulated in the preeclamptic placenta, where it may either have a nutritional effect or act as a modifier of signal transduction.
“…More recent studies have investigated the proteome of semen (Li et al, 2007), identified semen biomarkers of varying fertility rates (Peddinti et al, 2008), and examined inter-individual variations in the seminal plasma proteome of fertile men (Yamakawa et al, 2007). Studies have been conducted to determine the proteins in common in oocytes and ovarian cumulus cells that may be involved in the communication process for maturation (Memili et al, 2007), to determine biomarkers of preeclampsia by evaluation of amniotic fluid of healthy vs hypertensive, or preeclamptic women (Park et al, 2008), and to study mammalian preimplantation and postimplantation embryonic development (Katz-Jaffe et al, 2005). Proteomics has been included in the study of bisphenol A-induced alterations in the proteome of prenatally exposed mice (Yang et al, 2008).…”
This study was conducted to evaluate the use of metabolomics for improving our ability to draw correlations between early life exposures and reproductive and/or developmental outcomes. Pregnant CD rats were exposed by gavage daily during gestation to vehicle or to butylbenzyl phthalate (BBP) in vehicle at a level known to induce effects in the offspring and at a level previously not shown to induce effects. Urine was collected for 24 h (on dry ice using all glass metabolism chambers) from dams on gestational day 18 (during exposure) and on post natal day (pnd) 21, and from pnd 25 pups. Traditional phenotypic anchors were measured in pups (between pnd 0 and pnd 26). Metabolomics of urine collected from dams exposed to vehicle or BBP exhibited different patterns for endogenous metabolites. Even three weeks after gestational exposure, metabolic profiles of endogenous compounds in urine could differentiate dams that received the vehicle, low dose, or high dose of BBP. Metabolic profiles could differentiate male from female pups, pups born to dams receiving the vehicle, low or high BBP dose, and pups with observable adverse reproductive effects from pups with no observed effects. Metabolites significant to the separation of dose groups and their relationship with effects measured in the study were mapped to biochemical pathways for determining mechanistic relevance. The application of metabolomics to understanding the mechanistic link between low levels of environmental exposure and disease/dysfunction holds huge promise, because this technology is ideal for the analysis of biological fluids (e.g., urine, serum) in human populations.
“…Review articles, studies that did not use proteomic techniques or studies that did not compare PE with a normotensive (control) group were excluded. Moreover, studies involving animals only, studies presenting protein m/z values only rather than protein identifications, or those studies that compared different proteomic approaches were further excluded, leaving 16 primary studies eligible for this review ( Watanabe et al , 2004 ; Vascotto et al , 2007 ; Buhimschi et al , 2008 ; Jin et al , 2008 ; Park et al , 2008 ; Blankley et al , 2009 ; Blumenstein et al , 2009a , b ; Centlow et al , 2010 ; Gharesi-Fard et al , 2010 ; Rasanen et al , 2010 ; Johnstone et al , 2011 ; Liu et al , 2011 ; Epiney et al , 2012 ; Kolla et al , 2012 ; Myers et al , 2013 ). Figure 1 Flowchart showing selection of studies included in the systematic review.…”
STUDY QUESTIONDo any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS).SUMMARY ANSWERFive previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls.WHAT IS KNOWN ALREADYVarious studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known.STUDY DESIGN, SIZE, DURATIONA systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013.PARTICIPANTS/MATERIALS, SETTING, METHODSIn all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192.MAIN RESULTS AND THE ROLE OF CHANCEFive proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies.LIMITATIONS, REASONS FOR CAUTIONThe techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues.WIDER IMPLICATIONS OF THE FINDINGSThis data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital.STUDY FUNDING/COMPETING INTEREST(S)No financial support was obtained for this project. There are no conflicts of interest.
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