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Abstract
The intra-uterine components of labor, namely, myometrial contractility, cervical ripening, and decidua/membrane activation, have been extensively characterized and involve a local pro-inflammatory milieu of cellular and soluble immune mediators. Targeted profiling has demonstrated that such processes extend to the intra-amniotic space, yet unbiased analyses of the proteome of human amniotic fluid during labor are lacking. Herein, we utilized an aptamer-based platform to characterize 1,310 amniotic fluid proteins and found that the proteome undergoes substantial changes with term labor (251 proteins with differential abundance, q < 0.1, and fold change > 1.25). Proteins with increased abundance in labor are enriched for immune and inflammatory processes, consistent with prior reports of labor-associated changes in the intra-uterine space. By integrating the amniotic fluid proteome with previously generated placental-derived single-cell RNA-seq data, we demonstrated the labor-driven upregulation of signatures corresponding to stromal-3 and decidual cells. We also determined that changes in amniotic fluid protein abundance are reflected in the maternal plasma proteome. Collectively, these findings provide novel insights into the amniotic fluid proteome in term labor and support its potential use as a source of biomarkers to distinguish between true and false labor by using maternal blood samples.
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1 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA; Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
2 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA (GRID:grid.254444.7); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807); 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); Wayne State University School of Medicine, Department of Biochemistry, Microbiology and Immunology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
3 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA (GRID:grid.254444.7); 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 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA (GRID:grid.254444.7); Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
5 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA (GRID:grid.254444.7); Research Centre for Natural Sciences, Systems Biology of Reproduction Research Group, Institute of Enzymology, Budapest, Hungary (GRID:grid.425578.9) (ISNI:0000 0004 0512 3755); Maternity Private Clinic, Budapest, Hungary (GRID:grid.425578.9); Semmelweis University, Department of Obstetrics and Gynecology, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821)
6 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA (GRID:grid.11804.3c); 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)
7 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA (GRID:grid.254444.7); 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)
8 Wayne State University College of Engineering, Department of Biomedical Engineering, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
9 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, NICHD/NIH/DHHS, Pregnancy Research Branch, Detroit, USA (GRID:grid.254444.7); 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)