Progesterone Modulates Placental Expression of p53 and β-Catenin in a Zone-Specific Manner in Dexamethasone-Treated Rats.

Introduction The placenta is a transient pregnancy organ, and its development depends on proliferation and apoptosis throughout pregnancy. Abnormal placental development can result in intrauterine growth restriction (IUGR). Progesterone has a major role in regulating cell death and survival in various tissues, and its low maternal levels are highly correlated with IUGR. Aim The aim of this article was to evaluate the modulatory effect of progesterone on placental cell death and survival in a rat model of dexamethasone-induced IUGR. Methods Pregnant Sprague-Dawley rats were treated with a daily intraperitoneal (i.p.) injection: control (saline), dexamethasone, dexamethasone and progesterone, and progesterone. Injections started from 15 days of gestation (dg) until the end of the experiment at 21 days of gestation. The fetus and the placenta were weighed, and the placental labyrinth and basal zones were weighed and taken for gene and protein analysis of p53 and β-catenin. Key results Dexamethasone treatment resulted in decreased maternal progesterone levels, and fetal body and placental basal and labyrinth zone weights. Dexamethasone treatment significantly increased p53 expression in the basal and labyrinth zones and decreased β-catenin expression in the basal zone only. Progesterone co-supplementation with dexamethasone alleviated the increase in p53 levels in the labyrinth zone only and restored the expression of β-catenin in the basal zone. Conclusion Despite progesterone modulation of cell survival and growth, the effect was not translated into improved fetal or placental weights. Implication: These results highlight the importance of the zone-specific effect of progesterone in modulating cell death and survival in the placental complications.