UZH-Logo

Late-gestational systemic hypoxia leads to a similar early gene response in mouse placenta and developing brain


Trollmann, R; Rehrauer, H; Schneider, C; Krischke, G; Huemmler, N; Keller, S; Rascher, W; Gassmann, M (2010). Late-gestational systemic hypoxia leads to a similar early gene response in mouse placenta and developing brain. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 299(6):1489-1499.

Abstract

Late-gestational intrauterine hypoxia represents is a well known risk factor of acquired perinatal brain injury. Cell type- and age-specific sensitivity of hypoxia-responsive genes to low oxygen partial pressure is to be considered in the screening for early indicators of feto-placental tissue hypoxia. To identify early hypoxia-induced alterations in gene expression during late-gestational hypoxia (6 % O(2), 6 h; gestational day 20) we compared primary mouse placenta and brain transcriptomes using high-density oligonucleotide microarrays. Up-regulation of candidate marker genes for hypoxia was confirmed by quantitative RT PCR and immunohistochemistry. Both developing brain and placenta were highly responsive to systemic hypoxia at the level of gene expression involving hypoxia-inducible transcription factor (HIF)-dependent genes and immediate early genes (IEG) (Fos, Jun, Egr1, Bhlhb2), apoptosis-promoting factors (Bnip3, Dusp1, Ier3) which were all up-regulated, and genes modulating RNA binding and translation (Rbm3, Thap2, Lig4, Rbm12b) which mainly were down-regulated. Functional activity of the HIF system was obvious from elevated expression of various known HIF target genes (Adm, Vegf, Hk2, Pdk1, Bnip3, Ier3, Dusp-1) indicating immediate availability among early response to acute hypoxia. In addition, genes not yet described as being hypoxia-related were identified that are involved in angiogenesis/cell differentiation (Gna13, Gab2), mRNA processing and embryonic development. RT PCR of placenta and brain tissues confirmed up-regulation of selected HIF target genes and IEG. These data indicate that the early hypoxia-induced genomic response of the placenta mirrors that of developing brain in a temporally parallel manner. Our observations implicate future diagnostic options to identify fetal and cerebral tissue hypoxia.

Late-gestational intrauterine hypoxia represents is a well known risk factor of acquired perinatal brain injury. Cell type- and age-specific sensitivity of hypoxia-responsive genes to low oxygen partial pressure is to be considered in the screening for early indicators of feto-placental tissue hypoxia. To identify early hypoxia-induced alterations in gene expression during late-gestational hypoxia (6 % O(2), 6 h; gestational day 20) we compared primary mouse placenta and brain transcriptomes using high-density oligonucleotide microarrays. Up-regulation of candidate marker genes for hypoxia was confirmed by quantitative RT PCR and immunohistochemistry. Both developing brain and placenta were highly responsive to systemic hypoxia at the level of gene expression involving hypoxia-inducible transcription factor (HIF)-dependent genes and immediate early genes (IEG) (Fos, Jun, Egr1, Bhlhb2), apoptosis-promoting factors (Bnip3, Dusp1, Ier3) which were all up-regulated, and genes modulating RNA binding and translation (Rbm3, Thap2, Lig4, Rbm12b) which mainly were down-regulated. Functional activity of the HIF system was obvious from elevated expression of various known HIF target genes (Adm, Vegf, Hk2, Pdk1, Bnip3, Ier3, Dusp-1) indicating immediate availability among early response to acute hypoxia. In addition, genes not yet described as being hypoxia-related were identified that are involved in angiogenesis/cell differentiation (Gna13, Gab2), mRNA processing and embryonic development. RT PCR of placenta and brain tissues confirmed up-regulation of selected HIF target genes and IEG. These data indicate that the early hypoxia-induced genomic response of the placenta mirrors that of developing brain in a temporally parallel manner. Our observations implicate future diagnostic options to identify fetal and cerebral tissue hypoxia.

Citations

8 citations in Web of Science®
8 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

2 downloads since deposited on 18 Jan 2011
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:18 Jan 2011 09:55
Last Modified:05 Apr 2016 14:25
Publisher:American Physiological Society
ISSN:0363-6119
Publisher DOI:10.1152/ajpregu.00697.2009
PubMed ID:20926767
Permanent URL: http://doi.org/10.5167/uzh-38599

Download

[img]
Content: Accepted Version
Filetype: PDF - Registered users only
Size: 2MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations