81 - Notch Signaling and Intrauterine Growth Restriction in Rats: Is There a Modulatory Role for Melatonin?

Poster Board Number: 81
There are separate poster presentation times for odd and even posters.
Odd poster #s – first hour
Even poster #s – second hour

Abstract Body : Introduction& Objectives: Notch signaling is involved in cell proliferation, differentiation, and death. Recent research indicates that there is an important role in the Notch signaling pathway in normal fetal development and placental functions. However, molecular mechanisms that regulate the Notch signaling pathway during placental growth are obscure. Melatonin, an antioxidant, and hormone, imparts neuroprotective and cardioprotective effects on fetuses when pregnancies are complicated by intrauterine growth restriction (IUGR). In this study, we ask the question of whether the Notch signaling pathway genes that would translate into Notch proteins and their receptors get dysregulated by dexamethasone-induced IUGR and if melatonin supplementation beneficially re-regulates the genes in the rats.
Methods: Pregnant Sprague-Dawley rats (n=6/group) were divided into a normal saline control group, a normal saline and melatonin-supplemented group, a dexamethasone-induced IUGR group, and an IUGR group supplemented with melatonin. Pregnant rats were administered dexamethasone (0.2 mg/kg/d; IP) or saline from gestation days 15-18 or 15-20. Melatonin-supplemented groups were administered 0.01% melatonin mixed in drinking water during the entire gestation period until the sample collection on gestation days 19 and 21. The Notch signaling pathway genes were estimated by RT2 Profiler™ PCR array in the placentas' labyrinth and basal zones.
Results: In this IUGR model, the maternal body weight, placental, and fetal weights were reduced on gestation days 19 and 21 (P< 0.05). However, melatonin did not recover the lost body and placental weight. In IUGR placentas, DII3, Jag2, and ADAM10 genes were up-regulated in the labyrinth zone, whereas Notch 2, Jag1, Jag2, ADAM17, Ncstn, Psen 1, Psen2, and HeyL genes were up-regulated in the basal zone (P< 0.05). Melatonin supplementation recovered the expression levels of the aforementioned genes in the placentas (P< 0.05).
Conclusion: Up-regulated Notch signaling in the placentas is associated with dexamethasone-mediated growth restriction in rats. Although melatonin does not recover the lost body and placental weights, it re-regulates the dysregulated Notch signaling pathway genes in rats.