Effect of hypoxia on the expression of pro- and anti-apoptotic proteins in neuronal nuclei of the guinea pig fetus during gestation.

The present study investigates the expression of apoptotic proteins Bax, Bad, Bcl-2, and Bcl-xl following hypoxia in the cerebral cortex of the guinea pig fetus as a function of gestational age. Normoxic (Nx, n = 6) and hypoxic (Hx, n = 6) guinea pig fetuses at 35 and 60 days gestation were studied. Bax expression (OD X mm(2)) was 96.9 +/- 9.5 (Nx 35 days), 116.5 +/- 8.3 (Hx 35 days), P < 0.05 and 116.2 +/- 3.4 (Nx 60 days, 144.6 +/- 11.7 (Hx 60 days), P < 0.05. Bad expression (OD X mm(2)) was 78.6 +/- 2.6 (Nx 35 days), 102.9 +/- 5.8 (Hx 35 days), P < 0.05 and 101.5 +/- 4.3 (Nx 60 days), 139.8 +/- 7.9 (Hx 60 days), P < 0.05 vs. Nx 60 days, also significantly higher from preterm hypoxia P < 0.007. Expression of Bcl-2 (OD X mm(2)) was 27.4 +/- 2.0 (Nx 35 days), 28.0 +/- 2.4 (Hx 35 days), and 27.4 +/- 2.7 (Nx 60 days), 29.7 +/- 2.3 (Hx 60 days). Expression of Bcl-xl (OD X mm(2)) was 51.0 +/- 4.4 (Nx 35 days), 46.1 +/- 8.0 (Hx 35 days) and 50.0 +/- 1.4 (Nx 60 days), 54.9 +/- 7.4 (Hx 60 days). Hypoxia resulted in increased expression of the proapoptotic proteins Bax and Bad by 20% and 30% in the preterm as compared to 24% and 38% at term, without altering the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl. We conclude that the hypoxia-induced increased expression of Bax and Bad is greater at term compared to preterm. Furthermore, the hypoxia-induced increase in proapoptotic as compared to antiapoptotic proteins at term will accelerate the ongoing active process of programmed cell death at term compared to preterm gestation.