4.5 Article

Transcriptome changes in maternal peripheral blood during term parturition mimic perturbations preceding spontaneous preterm birth

Journal

BIOLOGY OF REPRODUCTION
Volume 106, Issue 1, Pages 185-199

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioab197

Keywords

cervix; chorioamniotic membranes; fetal membranes; immune response; inflammation; myometrium; parturition; placenta; preterm labor; uterus

Funding

  1. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and
  2. NICHD/NIH/DHHS [HHSN275201300006C]
  3. Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health

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By analyzing the transcriptomic data, it was found that women undergoing term labor exhibit labor-specific gene expression changes in their peripheral blood, which correlate with gene changes in the chorioamniotic membranes, myometrium, and cervix, partially overlapping with changes observed in asymptomatic women prior to preterm birth, potentially serving as a tool for assessing labor status and identifying preterm birth risk.
The complex physiologic process of parturition includes the onset of labor, which requires the orchestrated stimulation of a common pathway involving uterine contractility, cervical ripening, and chorioamniotic membrane activation. However, the labor-specific processes taking place in these tissues have limited use as predictive biomarkers unless they can be probed in non-invasive samples, such as the peripheral blood. Herein, we utilized a transcriptomic dataset to assess laborspecific changes in the peripheral blood of women who delivered at term. We identified a set of genes that were differentially expressed with labor and enriched for immunological processes, and these gene expression changes were strongly correlated with results from prior studies, providing in silico validation of our findings. We then identified significant correlations between labor-specific transcriptomic changes in the maternal circulation and those detected in the chorioamniotic membranes, myometrium, and cervix of women at term, demonstrating that tissue-specific labor signatures are partly mirrored in the peripheral blood. Finally, we demonstrated a significant overlap between the peripheral blood transcriptomic changes in term parturition and those observed in asymptomatic women, prior to the diagnosis of preterm prelabor rupture of the membranes, who ultimately delivered preterm. Collectively, we provide evidence that the normal process of labor at term is characterized by a unique immunological expression signature, which may serve as a useful tool for assessing labor status and for potentially identifying women at risk for preterm birth. Summary sentence: The maternal peripheral blood transcriptome undergoes labor-specific changes that correlate with those in the chorioamniotic membranes, myometrium, and cervix and partially overlap with those observed in asymptomatic women prior to preterm birth.

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