486: Intrauterine resuscitation with oxygen increases expression of oxidative stress genes in the male rat brain

Abstract

Maternal oxygen administration is one of the most widely practiced interventions for intrauterine fetal resuscitation. Whether such oxygen therapy induces oxidative stress, especially in the lipid-rich fetal brain, remains unknown. Here, we used a pregnant rat model of oxytocin-induced fetal distress to address this question and to determine if the consequences were sex-dependent. All experiments were approved by the Institutional Animal Care and Use Committee. Term pregnant SD rats (gestational day 20) were administered 100 mcg/kg i.v oxytocin to induce transient uterine tetany followed by immediate resuscitation with either room air or 100% oxygen for 6 h (N=8 dams/treatment). Male and female fetal brains were subsequently evaluated for biomarkers of oxidative stress (4-hydroxynonenal, protein carbonyl, 8-hydroxy-2’-deoxyguanosine), anti-oxidant status (GSSG/GSH glutathione ratio), and expression of oxidative stress genes with TaqMan® RT-qPCR. Data were analyzed with 2-way ANOVA with Sidak’s multiple comparisons test and presented as mean ± SEM (*p< 0.05, **p< 0.01). All pups survived the aberrant uterine contractility paradigm. There were neither treatment nor sex-related differences in either 4-hydroxynonenal, protein carbonyl, 8-hydroxy-2’-deoxyguanosine, or GSSG/GSH level in the fetal brain (Fig 1). Of the 28 oxidative stress genes investigated, 7 genes (ucp3, nox1, sod3, cat, prdx3, txnrd2, and mtcyb) were significantly upregulated with 100% oxygen, of which 5 were differentially upregulated only in the male fetal brain (nox1, sod3, cat, prdx3, and txnrd2) (Fig 2). The increased male-specific expression of nox1 and anti-oxidant genes (sod3, cat, prdx3, and txnrd2) suggest that the effects of maternal oxygen administration after uterine tetany could be sex-dependent. Further research is needed to understand if maternal oxygen administration, tachysystole, or both result in this apparent sex-dependent response.View Large Image Figure ViewerDownload Hi-res image Download (PPT)