Maternal serum proteome changes between the first and third trimester of pregnancy in rural Southern Nepal

Abstract

Characterization of normal changes in the serum proteome during pregnancy may enhance understanding of maternal physiology and lead to the development of new gestational biomarkers of health. In 23 Nepalese pregnant women who delivered at term two-dimensional difference in-gel electrophoresis (DIGE) was used to assess changes in relative protein abundance between paired serum samples collected in the first and third trimesters. One-hundred and forty-five of over 700 protein spots in DIGE gels (pI 4.2–6.8) exhibited nominally significant (p<0.05) differences in abundance across trimesters. Additional filtering using a Bonferroni correction reduced the number of significant (p<0.00019) spots to 61. Mass spectrometric analysis detected 38 proteins associated with gestational age, cytoskeletal remodeling, blood pressure regulation, lipid and nutrient transport, and inflammation. One new protein, pregnancy-specific β-glycoprotein 4 was detected. A follow-up isotope tagging for relative and absolute quantitation (iTRAQ) experiment of six mothers from the DIGE study revealed 111 proteins, of which 11 exhibited significant (p<0.05) differences between trimesters. Four of these proteins: gelsolin, complement C1r subcomponent, α-1-acid glycoprotein, and α-1B-glycoprotein also changed in the DIGE analysis. Although not previously associated with normal pregnancy, gelsolin decreased in abundance by the third trimester (p<0.01) in DIGE, iTRAQ and Western analyses. Changes in abundance of proteins in serum that are associated with syncytiotrophoblasts (gelsolin, pregnancy specific β-1 glycoprotein 1 and β-2-glycoprotein I) probably reflect dynamics of a placental proteome shed into maternal circulation during pregnancy. Measurement of changes in the maternal serum proteome, when linked with birth outcomes, may yield biomarkers for tracking reproductive health in resource poor settings in future studies.

Aflatoxin exposure during the first 1000 days of life in rural South Asia assessed by aflatoxin B1-lysine albumin biomarkers

“…This research was initiated by an analysis of aflatoxin B 1 -lysine albumin adducts in a pooled sample representing one thousand 6–7 year old children in Sarlahi, Nepal who were being analyzed for plasma proteome differences related to micronutrient status (Scholl et al, 2012). That analysis showed 56.5 pg aflatoxin B 1 -lysine/mg albumin, prompting the more detailed examination of aflatoxin exposure during pregnancy and early life described here.…”

“…An initial analysis of aflatoxin-albumin adducts in a pooled sample from one thousand 6–7 year old children in Nepal found 56.5 pg aflatoxin B 1 -lysine/mg albumin, a level comparable to that detected in very nutritionally compromised children in West Africa when the different method of analyses are considered (Gong et al, 2004; McCoy et al, 2008). This biomarker observation prompted a more detailed examination using samples already analyzed for its plasma proteome that had collected during the first and third trimester of pregnancy of women enrolled in a randomized micronutrient intervention clinical trial in Sarlahi, Nepal (Cole et al, 2013; Scholl et al, 2012). …”

Host Immune Status and Response to Hepatitis E Virus Infection

“…A proteome analysis conducted in a cohort of pregnant women in southern Nepal identified changes from the first to third trimesters in the expression of proteins, some of which had not previously been reported in studies of healthy pregnant women (354). Several proteins whose expression differed significantly between the first and third trimesters were associated with immune function and inflammation, including gelsolin, pregnancy zone, plasma protease C1 inhibitor, and various complement-related subcomponents, as well as other proteins whose functions remain uncertain (354). Environmentally and genetically mediated differences in immune system modulation over the course of pregnancy could help explain regional differences in the observed hepatitis E incidence and severity during pregnancy.…”

“…Pregnant women elsewhere in South Asia are often deficient in several micronutrients, and seasonal food availability may exert a major influence on maternal micronutrient status (353). A proteome analysis conducted in a cohort of pregnant women in southern Nepal identified changes from the first to third trimesters in the expression of proteins, some of which had not previously been reported in studies of healthy pregnant women (354). Several proteins whose expression differed significantly between the first and third trimesters were associated with immune function and inflammation, including gelsolin, pregnancy zone, plasma protease C1 inhibitor, and various complement-related subcomponents, as well as other proteins whose functions remain uncertain (354).…”

Low abundance plasma proteins in labour

“…It is possible that different pathways interact with each other and that other as yet unknown factors are involved. The advent of reliable proteomics methodology has opened a new window of opportunity in the study of human parturition by allowing the simultaneous study of multiple proteins in complex biological samples (Pereira et al 2007, Scholl et al 2012. The need for clinically useful biomarkers to predict preterm labour remains (Conde-Agudelo et al 2011).…”