title: 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. 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.
authors.affiliation: Johns Hopkins University, Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 N. Wolfe St., Baltimore, MD 21205-2200, USA. peter.scholl@fda.hhs.gov
authors.forename: P F
authors.initials: PF
authors.lastname: Scholl
authors.forename: R N
authors.initials: RN
authors.lastname: Cole
authors.forename: I
authors.initials: I
authors.lastname: Ruczinski
authors.forename: M
authors.initials: M
authors.lastname: Gucek
authors.forename: R
authors.initials: R
authors.lastname: Diez
authors.forename: A
authors.initials: A
authors.lastname: Rennie
authors.forename: C
authors.initials: C
authors.lastname: Nathasingh
authors.forename: K
authors.initials: K
authors.lastname: Schulze
authors.forename: P
authors.initials: P
authors.lastname: Christian
authors.forename: J D
authors.initials: JD
authors.lastname: Yager
authors.forename: J D
authors.initials: JD
authors.lastname: Groopman
authors.forename: K P
authors.initials: KP
authors.lastname: West
mesh_terms: D015153:Blotting, Western; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D044342:Malnutrition; D013058:Mass Spectrometry; D009390:Nepal; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011263:Pregnancy Trimester, Third / Q000097:blood*; D020543:Proteome; D012424:Rural Population; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D020543:Proteome