Progesterone receptor isoform expression in the guinea pig myometrium from normal and growth restricted pregnancies

Despite the increased incidence of preterm labor with intrauterine growth restriction, the mechanisms of the relationship are unclear. In women, functional progesterone withdrawal mediated by changing myometrial progesterone receptor (PR) expression is linked to labor. The objectives of this study were to assess myometrial PR isoform abundance in guinea pig pregnancies associated with growth restriction, induced by disruption of placental blood supply, and in nongravid uterine horns during late gestation and with labor. Myometrial progesterone receptor isoform A (PRA) and B (PRB) abundance were downregulated as labor approached and the expression of both isoforms were markedly higher in the nongravid compared to the gravid uterine horns. The fall in myometrial PRA and B protein levels was delayed in intrauterine growth-restricted (IUGR) pregnancies despite these pregnancies delivering significantly earlier. The results suggest a PR-mediated functional progesterone withdrawal mechanism in guinea pigs that may initiate uterine activation but does not directly stimulate labor and an unexpected role of PR regulation in IUGR-associated pregnancies.