The Role of Progesterone Receptor Isoform Expression in Determining Uterine Quiescence and Preterm Labour Susceptibility in Nigerian Women

Progesterone maintains uterine quiescence through receptor-mediated signalling, and shifts in progesterone receptor (PR) isoform ratios, particularly PR-A/PR-B balance, are implicated in the initiation of labour, but the expression patterns of PR isoforms in term and preterm labour myometrium from Nigerian women have not been characterised. This dissertation investigates progesterone receptor isoform expression and its relationship to uterine quiescence and preterm labour susceptibility in Nigerian women. Myometrial biopsies were collected from four groups at teaching hospitals in Enugu (South East) and Plateau (North Central): women in preterm labour (n=30), preterm not in labour (n=30), term in labour (n=30), and term not in labour (n=30). PR-A and PR-B protein expression was quantified by Western blot and immunohistochemistry. PR-A/PR-B mRNA ratio was determined by quantitative RT-PCR. Functional assays examined progesterone-mediated suppression of oxytocin-induced myometrial contractility in organ bath experiments. PR-A/PR-B ratio was significantly higher in preterm labour samples than term in-labour samples, indicating relative PR-A dominance in preterm labour. Progesterone-mediated contractility suppression was significantly less effective in myometrium from preterm labour samples, consistent with functional progesterone resistance. Promoter methylation analysis identified PR-B promoter hypermethylation in preterm labour samples, providing an epigenetic mechanism for isoform ratio dysregulation. The dissertation advances mechanistic understanding of Nigerian-population progesterone receptor biology and identifies PR isoform ratio as a potential therapeutic target for preterm labour prevention. Keywords: progesterone receptor, preterm labour, uterine quiescence, isoform expression, Nigeria