Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition

Objective: The role of progesterone in the control of human parturition remains unsettled. Because there is no systemic progesterone withdrawal before the onset of labor, a 'functional progesterone withdrawal' has been proposed to be operative before human parturition. This may be accomplished by a change in the density of the progesterone receptor (PR) isoforms in myometrium and fetal membranes. The purpose of our study was to determine if spontaneous term labor is associated with changes of PR isoforms (PR-A and PR-B) in the fetal membranes. Study design: Fetal membranes were obtained from women undergoing elective cesarean delivery at term (not in labor group), and from women with a vaginal delivery (labor group). The expression of PR isoforms was assessed by Western blot analysis of amnion and chorio-decidua. Densitometric analysis of PR-A/PR-B ratio was performed. Immunohistochemistry with specific antibodies to PR-A and PR-B was done. Nonparametric statistics were used for analysis. Results: 1) The predominant isoform of PR in women not in labor was PR-B, and PR-A in patients in labor. The ratio of PR-A/PR-B in fetal membranes was significantly higher in women in labor than in those not in labor (for amnion, median 4.3, range [0.9-8.4] vs median 0.4, range [0.3-2.6], P < .001; for chorio-decidua, median 2.0, range [1.1-19.2] vs median 1.2, range [0.1-2.0], P < .05). 2) Fetal membranes expressed both types of PR. 3) Immunohistochemistry showed the presence of PR-A and PR-B in the cytoplasm of amnion epithelial cells, chorion trophoblast, and decidual cells. Conclusion: Human parturition at term is associated with changes in PR isoforms in the fetal membranes and, thus, a local 'functional progesterone withdrawal' may operate in human parturition through this mechanism.