Endocrine Abstracts

Introduction and objectives: Placental apoptosis plays important roles in both normal physiological and abnormal pathological placental development. Fetal growth is highly dependent on the placenta, thus any disruption in placental formation may lead to intrauterine growth restriction (IUGR). The rat placenta consists of a basal zone (BZ) and labyrinth zone (LZ). The BZ is the major site of placental hormone production and it goes under physiological apoptosis at the end of term. While the LZ is the major site for nutrient/waste exchange which is essential till the end of term. Dexamethasone (DEX) is a synthetic glucocorticoid that stimulates placental apoptosis and inhibits feto-placental growth which leads to IUGR. Research on rats indicated that DEX-induced IUGR is associated with placental apoptosis. In the LZ of IUGR placentas the activity of p53 a tumor suppressor protein that initiate apoptosis is increased. Progesterone (P), on the other hand, has been shown to inhibit placental apoptosis. Furthermore, research conducted on human and rat placentas showed that low maternal progesterone level during pregnancy is associated with low fetal and placental weights and development of IUGR. We hypothesize that P will reverse the apoptotic effects of DEX-induced IUGR

Methods: Pregnant Sprague-Dawley rats received daily intra-peritoneal injections of either saline (C group), DEX (0.2 mg/kg; DEX group), P (5 mg/Kg/day: P group) or mixture of DEX + P (0.2 mg/kg + 5 mg/Kg/day: DEX+P group) starting from 15 days of gestation (dg) to 21 dg. Gene and protein expressions of p53 in the BZ and LZ were investigated by RT-PCR and Western blotting in all groups.

Results: In BZ, DEX decreases the p53 mRNA and protein expression while P treatment increases it and returned it normal levels (P<0.05). p53 mRNA expression decreased also in DEX group compared to that in P (P<0.05). In P group, p53 protein expression was lower compared than in C and DEX+P (P<0.05). In the LZ, DEX increases the p53 mRNA and protein expression while P treatment decreases it but not to normal levels (P<0.05). p53 mRNA and protein expression was higher in P group compared to C (P<0.05). Also in P group p53 mRNA expression was higher than that in DEX+P, while the p53 protein expression was lower than that in DEX group (P<0.05).

Conclusions: In the LZ, P reduces the high level of p53 caused by DEX which could be associated with reduction in apoptosis.