The expression of Akt and ERK1/2 proteins decreased in dexamethasone-induced intrauterine growth restricted rat placental development

Abstract

The placenta is a complicated tissue that lies between maternal and fetal compartments. Although the architecture of the human and rodent placentas differ a little in their details, their overall structures and the molecular mechanisms of placental developments are thought to be very similar. In rats, fetal-placental exposure to maternally administered glucocorticoids decreases birth weight and placental weight. The mechanism underlying the placental growth inhibitory effects of glucocorticoids have not been elucidated. Moreover it is still not determined that how Akt and ERK1/2 proteins related proliferation and apoptosis mechanisms are influenced by dexamethasone-induced IUGR (Intrauterine Growth Restriction) placentas. The aim of this study was to investigate the expression levels and spatio-temporal immunolocalizations of Akt, p-Akt, ERK1/2 and p-ERK1/2 proteins in normal and dexamethasone treated placental development in pregnant Wistar rats. Pregnant rats were subcutaneously injected with 100 μg/kg dexamethasone 21-acetate in 0.1 ml 10% ethanol on day 10 and 12 of gestation. Afterwards injection was continued as 200 μg/kg until they were killed on day 12 (injection started on day 10), 14, 16, 18 and 20 (injections started on day 12) of pregnancy. Placental and embryonal tissues were collected for immunohistochemistry and Western blot analysis. We found that maternal dexamethasone treatment led to a decrease in ERK1/2 and Akt activation during rat placental development. The decrease in Akt and ERK1/2 activations may result with cell survival inhibition or apoptosis stimulation. Hence, dexamethasone induced placental and embryonal developmental abnormalities could be associated with reduction of Akt and ERK1/2 activation.

Glucocorticoid exposure altered angiogenic factor expression via Akt/mTOR pathway in rat placenta

“…In our previous study, we have shown that p-Akt expression was decreased in placentas of DEX treated rats (Ozmen et al, 2011). With our recent study we have both confirmed our previous results and also observed that not only Akt activation but also p70S6K and 4EBP1 activations were decreased by glucocorticoid overexposure.…”

“…Control and IUGR groups were generated as previously described (Ozmen et al, 2011). IUGR-inducing dosages of Dexamethasone 21-acetate (Sigma) in rats were selected as previously demonstrated (Benediktsson et al, 1993).…”

“…Rat placental lysates (mesometrial triangle were excluded) were prepared and total cellular protein was separated by SDS polyacrylamide gel electrophoresis as previously described by Ozmen et al (2011). Membranes were incubated with VEGF (Millipore), VEGFR1 (Millipore), VEGFR2 (Cell Signaling), PIGF (Santa Cruz), p-p70S6K (Thr389) (Cell Signaling), p70S6K (Cell Signaling), p-4EBP1 (Thr37/46) (Cell Signaling), 4EBP1 (Cell Signaling), p-Akt (Ser473) (Cell Signaling), Akt (Cell Signaling) and Beta Actin (Abcam) antibodies +4 • C overnight.…”

The Effects of Glucocorticoids on Fetal and Placental Development

“…The decrease in ERK1/2 and Akt activation may result in cell survival inhibition or apoptosis stimulation. Consequently, Dex induced placental and embryonal developmental abnormalities could be associated with reduction of Akt and ERK1/2 activation [91]. In another study, decreased levels of placental Akt phosphorylation was observed after in utero exposure to Dex [92].…”

“…HUVECs were cultured at different concentrations (0. In another study of ours, we investigated the effects of glucocorticoids on rat placental development depending on the PI3K/Akt and MAPK-ERK1/2 pathways [91]. It was observed that, the IUGR group had significantly smaller embryos on day 20 of gestation and had smaller placentas on day 14, 16, 18 and 20 compared with control.…”