Introduction: At the maternal fetal interface, the decidua may play a role in labor, a process which involves the prostaglandin (PG) pathway (important clinical target for labor management). However, the PG pathway is highly complex with three rate limiting steps, and its complexity remains to be addressed in the decidua. We hypothesize the decidua exhibits 1) a distinct expression profile of PG genes with labor, and 2) differential expression in preterm labor (PTL) compared to term labor.
Methods: Decidual samples dissected from the myometrium at cesarean section were used to assess PG gene expression by RNAseq and qRT-PCR (n=7 preterm non-labor, n=11 preterm labor, n=31 term non-labor, n=31 term labor patients). Expression analyses were conducted using student’s t-test, one-way ANOVA, and adjusted for multiple testing using the Benjamini-Hochberg method.
Results: RNAseq analysis identified 36 unique PG pathway genes expressed in decidua. The ratio of PG expression in laboring uteri to non-laboring uteri (L:NL) was greater in the preterm group (p=0.038). PTGS2 (secondary rate limiting step) expression was higher in laboring uteri compared to non-laboring (p<0.05) and was correlated with gestational age at delivery (p=0.0005). At term, we observe lower expression of PLA2 (primary rate limiting step) group 2D (p=0.048), while preterm labor is associated with lower expression of PLA2 subtypes 4C (p=0.024) and 16 (p=0.019). Expression of PLA2 groups 4A and 6 correlated negatively with gestational age at delivery (p>0.05).
Conclusion: Greater L:NL ratios in the preterm group indicates that PG expression may be involved in preparation for labor during the weeks leading to term. The expression of multiple PLA2 subtypes may offer the potential for fine tuning PG synthesis during labor, which occurs upstream of the current clinical targets. Further investigation of upstream enzymes may provide insight on the mechanism of PTL and highlight new potential targets for clinical management.
Moss Bruton Joe– MD Student, Physiology and Pharmacology, University of Calgary
Stephen Wood– Associate Professor, Obstetrics and Gynecology, University of Calgary
David Anderson– Instructor, Biochemistry and Molecular Biology, University of Calgary
Donna Slater– Assistant Professor, Physiology and Pharmacology, University of Calgary