Faculty Collaboration Database

Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats. Brain Res 2001 Mar 23;895(1-2):186-93

Date

03/22/2001

Pubmed ID

11259777

DOI

10.1016/s0006-8993(01)02074-1

Scopus ID

2-s2.0-0035937585 (requires institutional sign-in at Scopus site)   56 Citations

Abstract

Infants suffering uteroplacental insufficiency and hypoxic ischemic injury often demonstrate cerebral apoptosis. Our objective was to determine the global effects of uteroplacental insufficiency upon cerebral gene expression of the apoptosis related proteins Bcl-2 and Bax and their role in increasing vulnerability to hypoxia-induced cerebral apoptosis. We therefore caused uteroplacental insufficiency and growth retardation by performing bilateral uterine artery ligation upon pregnant rats 2 days prior to term delivery and elicited further perinatal fetal hypoxia by placing maternal rats in 14% FiO(2) 3 h prior to delivery. We quantified cerebral levels of Bcl-2 and Bax mRNA, lipid peroxidation, caspase-3 activity, and cAMP in control and growth retarded term rat pups that experienced either normoxia or hypoxia. Uteroplacental insufficiency alone caused a significant decrease in cerebral Bcl-2 mRNA levels without altering cerebral Bax mRNA levels, malondialdehyde levels, or caspase-3 activity. In contrast, uteroplacental insufficiency and subsequent fetal hypoxia significantly increased cerebral Bax mRNA levels, lipid peroxidation and caspase-3 activity; Bcl-2 mRNA levels continued to be decreased. Hypoxia alone increased cerebral cAMP levels, whereas uteroplacental insufficiency and subsequent hypoxia decreased cerebral cAMP levels. We speculate that the decrease in Bcl-2 gene expression increases the vulnerability towards cerebral apoptosis in fetal rats exposed initially to uteroplacental insufficiency and subsequent hypoxic stress.

Author List

Lane RH, Ramirez RJ, Tsirka AE, Kloesz JL, McLaughlin MK, Gruetzmacher EM, Devaskar SU

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Caspase 3
Caspases
Cerebral Cortex
Cyclic AMP
Female
Fetal Growth Retardation
Fetus
Gene Expression Regulation
Hypoxia, Brain
Lipid Peroxidation
Malondialdehyde
Neurons
Oxidative Stress
Placental Insufficiency
Pregnancy
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
Rats
Rats, Sprague-Dawley
bcl-2-Associated X Protein