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Abstract
The cell-free transcriptome in amniotic fluid (AF) has been shown to be informative of physiologic and pathologic processes in pregnancy; however, the change in AF proteome with gestational age has mostly been studied by targeted approaches. The objective of this study was to describe the gestational age-dependent changes in the AF proteome during normal pregnancy by using an omics platform. The abundance of 1310 proteins was measured on a high-throughput aptamer-based proteomics platform in AF samples collected from women during midtrimester (16–24 weeks of gestation, n = 15) and at term without labor (37–42 weeks of gestation, n = 13). Only pregnancies without obstetrical complications were included in the study. Almost 25% (320) of AF proteins significantly changed in abundance between the midtrimester and term gestation. Of these, 154 (48.1%) proteins increased, and 166 (51.9%) decreased in abundance at term compared to midtrimester. Tissue-specific signatures of the trachea, salivary glands, brain regions, and immune system were increased while those of the gestational tissues (uterus, placenta, and ovary), cardiac myocytes, and fetal liver were decreased at term compared to midtrimester. The changes in AF protein abundance were correlated with those previously reported in the cell-free AF transcriptome. Intersecting gestational age-modulated AF proteins and their corresponding mRNAs previously reported in the maternal blood identified neutrophil-related protein/mRNA pairs that were modulated in the same direction. The first study to utilize an aptamer-based assay to profile the AF proteome modulation with gestational age, it reveals that almost one-quarter of the proteins are modulated as gestation advances, which is more than twice the fraction of altered plasma proteins (~ 10%). The results reported herein have implications for future studies focused on discovering biomarkers to predict, monitor, and diagnose obstetrical diseases.
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1 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); Wayne State University College of Engineering, Department of Biomedical Engineering, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
2 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); University of Michigan, Department of Obstetrics and Gynecology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); Michigan State University, Department of Epidemiology and Biostatistics, East Lansing, USA (GRID:grid.17088.36) (ISNI:0000 0001 2150 1785); Wayne State University, Center for Molecular Medicine and Genetics, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); Detroit Medical Center, Detroit, USA (GRID:grid.413184.b) (ISNI:0000 0001 0088 6903)
3 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); Wayne State University School of Medicine, Department of Biochemistry, Microbiology and Immunology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
4 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
5 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); Wayne State University, Office of Women’s Health, Integrative Biosciences Center, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
6 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); Wayne State University, Center for Molecular Medicine and Genetics, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
7 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); The University of Texas Health Sciences Center at Houston, Department of Obstetrics, Gynecology & Reproductive Sciences, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401)
8 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); Wayne State University School of Medicine, Department of Physiology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); University of Arizona College of Medicine -Tucson, Department of Obstetrics & Gynecology, Tucson, USA (GRID:grid.134563.6) (ISNI:0000 0001 2168 186X)
9 Wayne State University College of Engineering, Department of Biomedical Engineering, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
10 National Institutes of Health, Perinatology Research Branch, US Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Detroit, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); Wayne State University College of Engineering, Department of Computer Science, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)