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Title: Impact of Prenatal Dexamethasone Administration on the Expression of p73 Gene Variants in Fetal Brain
Authors: Mai Abdullah Abul 
Supervisor: Dr. Abdeslam Mouihate
Keywords: Dexamethasone;p73 gene variants;Cell death program;Fetal developing brain
Issue Date: 2015
Publisher:  Kuwait university - college of graduate studies
Abstract: Synthetic glucocorticoids (GCs), such as dexamethasone (Dex) are clinically prescribed to pregnant woman at risk of preterm delivery, or bearing fetuses at risk of congenital adrenal hyperplasia. Prenatal Dex administration was associated with several neuropsychological and behavioral disorders during infancy and adulthood. The long lasting impact of prenatal GCs on fetal brain development is well known; however, the mechanisms through which prenatal GCs induce these long lasting disturbances are not discovered yet. Recently, prenatal GCs exposure was found to induce fetal brain growth restriction and changed the expression of one of the genes that are involved in neural cell death, survival, and differentiation programs: p73. p73 gene encodes for two protein variants; the pro-apoptotic protein (TAp73), and the anti-apoptotic protein (∆Np73). It is not clear how synthetic GCs modulate this gene and which neural brain cell types (neurons or glia) are affected. In this study, the impact of prenatal Dex on fetal brain development will be examined through detecting the expression and the neural location of p73 gene/protein variants. Pregnant dams received daily intra-peritoneal injection of either Dex (0.4 mg/kg, n = 6) or pyrogen-free saline (n = 6) from gestation day (GD) 14 until GD21. Fetal brains were collected and snap frozen in liquid nitrogen, then stored at -80°C until used for detection of TAp73 and ∆Np73 mRNAs and proteins through RTPCR and western blot respectively. Another group of fetal brains were immersed in buffered formalin solution 10% then, paraffin embedded to be used in immunohistochemistry study. Prenatal Dex administration during critical periods of fetal brain development (GD 14 – GD 21) significantly reduced fetal body as well as brain weight. Prenatal Dex increased TAp73 protein expression; this enhanced TAp73 expression was associated with pronounced neural cell death as revealed by increased cleaved caspase-3 immunoreactive cells. Furthermore, Dex significantly reduced the number of mature neurons co-expressing TAp73 protein. The increased expression of TAp73 and the concurrent increase in neural cell death and reduction in the number of differentiated neurons may be responsible for the restricted fetal brain development in Dex treated dams.
Appears in Programs:0530 Physiology (M.Sc.)

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