Labour is associated with decreased expression of the PGF2alpha receptor (PTGFR) and a novel PTGFR splice variant in human myometrium but not decidua.
The prostaglandin F(2α) receptor (PTGFR) is believed to play a role in the process of parturition. The main support for this comes from animal studies; however, in humans, the evidence is less clear. The gene coding for PTGFR may be subject to alternative splicing to generate alternate variants with different signalling pathways. We have determined regional (upper versus lower segment) and labour-associated expression of PTGFR mRNA and a recently identified splice variant of PTGFR in human myometrium and decidua. We also examined the effect of the inflammatory cytokine interleukin-1β (IL-1β) on PTGFR mRNA expression in a model of cultured human myometrial smooth muscle cells. We identified a PTGFR transcript variant 2 (PTGFR-v2) generated by alternate splicing in human myometrium and decidua. The PTGFR-v2 contains an additional 71 base pair exon, which results in a truncated protein at 297 amino acids compared with the PTGFR transcript variant 1 (PTGFR-v1) at 359 amino acids. In contrast to our hypothesis, we demonstrate that PTGFR-v1 and PTGFR-v2 mRNA expression is not significantly higher in upper segment compared with lower segment paired samples. We also show a labour-associated decrease in PTGFR-v1 and PTGFR-v2 mRNA expression in lower segment myometrial samples. IL-1β-stimulated mRNA expression of both PTGFR variants in a distinct time-dependent manner in myometrial cell cultures. We suggest that the role of the PTGFR in the human uterus requires further validation prior to pursuing it as a target for the treatment of preterm labour. In addition, the presence of distinct variants suggests further levels of gene regulation within the pregnant uterus.
Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, AB, Canada.
Andrea
A
Hay
Stephen
S
Wood
David
D
Olson
Donna M
DM
Slater
D017398:Alternative Splicing / Q000235:genetics*; D003656:Decidua / Q000378:metabolism*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D007743:Labor, Obstetric / Q000235:genetics*; D009215:Myometrium / Q000378:metabolism*; D011247:Pregnancy; D011982:Receptors, Prostaglandin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053583:Interleukin-1beta; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor