Exposure to synthetic glucocorticoids during pregnancy alters the expression of p73 gene variants in fetal brains in a sex-specific manner.

Abstract:

: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.

journal_name

Brain Res

journal_title

Brain research

authors

Abul M,Al-Bader MD,Mouihate A

doi

10.1016/j.brainres.2018.11.030

subject

Has Abstract

pub_date

2019-03-15 00:00:00

pages

117-123

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(18)30596-1

journal_volume

1707

pub_type

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