Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics.

Area of Science:

• Reproductive biology
• Genomics
• Molecular signaling

Background:

• Preterm birth (PTL) is a leading cause of infant mortality globally.
• Uterine hormonal and inflammatory signaling interplay in labor onset is not fully understood.
• Investigating uterine gene expression changes during labor is crucial for understanding PTL.

Purpose of the Study:

• To characterize temporal transcriptome changes in the mouse uterus preceding term and preterm labor.
• To compare murine labor-associated transcriptome changes with human data.
• To elucidate the roles of progesterone withdrawal and inflammation in labor initiation.

Main Methods:

• Murine models of term gestation, RU486-induced PTL, and lipopolysaccharide (LPS)-induced PTL were utilized.
• Myometrial tissue was collected at various gestational time points for RNA sequencing.
• RNA-Seq data were analyzed using multivariate modeling, pathway, and causal network analyses, and compared with human data.

Main Results:

• A core set of temporal myometrial gene changes was identified in mice for term and PTL.
• Progesterone withdrawal initiated labor without inflammation, while LPS-induced inflammation overrode progesterone's effects.
• Human labor transcriptomes more closely resembled inflammation-induced PTL in mice.

Conclusions:

• Inflammatory gene activation can induce labor in mice, but is not essential for labor itself.
• Human labor aligns more closely with LPS-induced PTL, suggesting a key role for inflammatory mediators in functional progesterone withdrawal.
• Understanding these transcriptomic changes can inform PTL prevention strategies.