A Transcriptomic Snapshot of Labor Timing and Development in Human Decidua

ABSTRACT: Introduction: Disruption in the synergistic machinery of human parturition can cascade into an ill-timed onset of labor, jeopardizing pregnancy outcomes and contributing to perinatal morbidity and mortality. Parturition is invoked by a phenotypic shift towards a pro-inflammatory predominant state; however, the mechanistic underpinnings as well as tissue-specific role and pathophysiological implications remain elusive. Predicting labor trajectory is further hindered due to confounding by concurrent processes either unrelated or exclusive to advancing gestation. It is thus critical to employ a strategic plan when probing the genetic and environmental tug-of-war that underlies parturition. Methods: We collected human deciduas to explore the genetic control of inflammation within the immunologically-distinct part of the placenta. We performed a genome-wide profiling of the trascriptome to incorporate environmental and fetal stimuli effects on phenotypic divergence. Samples were segregated into term labor (n=16), premature labor (n=16), and nonlaboring C-section (n=18) to distinguish between factors governing gestation duration and those involved in the final pathway of labor. Leveraging the high resolution of next-generation sequencing, we analyzed gene-, isoform-, and network scale-level variability across labor states and then interrogated clinical traits to extract key players in labor timing and development. Results: All samples exhibited a global upregulated expression of adhesion, vascular, humoral, and endocrine genes enriched in the placenta and critical to pregnancy sustenance. Nonlaboring deciduas revealed the most divergent transcriptional landscape, with significant enrichment for dysregulated vacular extracellular matrix remodeling and muscle contractility. Premature deciduas showed a more prominent immune-mediated fetal rejection, infection response, and lipid metabolism signature. Conclusion: Our study provides a comprehensive steady-state snapshot of co-/post-transcriptional changes across various modes of parturition. Using multilayered analytics, it suggests the withdrawal of immune suppression at the maternal-fetal interface during labor development, a process that is further enhanced with pre-existing intrauterine infection and systemic stress to potentially modulate labor timing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140602 | GEO | 2023/05/01

REPOSITORIES: GEO