Department of Physiology, Health Sciences Centre, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Department of Physiology, Health Sciences Centre, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Brain Res. 2019 Mar 15;1707:117-123. doi: 10.1016/j.brainres.2018.11.030. Epub 2018 Nov 23.
Fetal exposure to dexamethasone (DEX) alters brain plasticity and cognitive functions during adulthood in a sex-dependent manner. The mechanisms underlying such long-lasting sex-dependent change of prenatal DEX is not well understood. The p73 gene plays an important role in brain development. It encodes for two protein variants; the neural cell death protein (TAp73) and the anti-neural cell death protein (ΔNp73). Therefore, we sought to determine how prenatal exposure to DEX alters the expression of these p73 gene variants in the brain of male and female fetuses. Pregnant dams received daily injections of either DEX (0.4 mg/kg, i.p.) or saline from gestation day (GD) 14 until GD21. On GD21, body and brain weights were monitored and mRNA and protein levels of TAp73 and ΔNp73 were measured in male and female fetal brains using RT-PCR, Western blot, and immunohistochemistry. Prenatal exposure to DEX significantly reduced the body and brain weights of both male and female fetuses, although reduction in brain weight was less severe than that of the body weight. Administration of DEX to pregnant dams led to enhanced expression of both TAp73 and ΔNp73 gene/protein variants in the brain of male but not in that of female fetuses. Dexamethasone induced a sex-dependent effect on the expression of p73 gene variants. DEX-induced growth restriction in the brain of female fetuses is independent of p73 gene. This study strongly suggests that survival/death programs operate differently during the development of male and female brains.
胎儿暴露于地塞米松（DEX）以性别依赖的方式改变成年期大脑的可塑性和认知功能。 尚不清楚产前 DEX 这种持久的性别依赖性变化的潜在机制。 p73 基因在大脑发育中起重要作用。 它编码两种蛋白变体； 神经细胞死亡蛋白（TAp73）和抗神经细胞死亡蛋白（ΔNp73）。 因此，我们试图确定产前暴露于 DEX 如何改变雄性和雌性胎儿大脑中这些 p73 基因变体的表达。 妊娠母鼠从妊娠第 14 天（GD）至第 21 天（GD）每天接受 DEX（0.4mg/kg，ip）或生理盐水注射。 在 GD21 时，监测体重和脑重，并使用 RT-PCR、Western blot 和免疫组织化学测量雄性和雌性胎儿大脑中 TAp73 和 ΔNp73 的 mRNA 和蛋白水平。 产前暴露于 DEX 显著降低了雄性和雌性胎儿的体重和脑重，尽管脑重的减少比体重减少更为严重。 向孕鼠给予 DEX 导致雄性而不是雌性胎儿大脑中 TAp73 和 ΔNp73 基因/蛋白变体的表达增强。 DEX 对 p73 基因变体的表达具有性别依赖性影响。 DEX 诱导的雌性胎儿脑生长受限与 p73 基因无关。 这项研究强烈表明，存活/死亡程序在雄性和雌性大脑发育过程中以不同的方式起作用。
