Antenatal maternal hypoxic stress: Adaptations in fetal lung renin-angiotensin system

Ravi Goyal, Arthur Leitzke, Dipali Goyal, Ciprian P. Gheorghe, Lawrence D. Longo

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Antenatal maternal hypoxia (AMH) can lead to intrauterine growth restriction (IUGR), as well as idiopathic pulmonary hypertension of newborn and adult, the latter of which may be a consequence of alterations in the local pulmonary reninangiotensin system (RAS). Little is known of these adaptations, however. Thus, we tested the hypothesis that antenatal maternal hypoxia is associated with alterations in gene and protein expression of the pulmonary renin-angiotensin system, which may play an important role in pulmonary disorders in the offspring. In FVB/NJ mice, we studied messenger RNA (mRNA) and protein expression, as well as promoter DNA methylation and microRNA (miRNA) levels in response to 48 hours hypoxia (10.5% O2) at 15.5 day post coitum (DPC). In response to AMH, the pulmonary mRNA levels of angiotensin-converting enzyme (ACE) 1.2, ACE-2, and angiotensin II type 1b (AT-1b) receptors were increased significantly, as compared to controls (N = 4). In response to antenatal hypoxia, pulmonary protein levels of renin and ACE-2 also were increased significantly, whereas ACE-1 protein expression was reduced. In fetal lungs, we also observed reduced expression of the miRNAs: mmu-mir -199b, -27b, -200b, and -468 that putatively increase the translation of renin, ACE-1, ACE-2, and AT-1 receptors, respectively. In response to AMH, promotermethylation of ACE was unchanged.We conclude that AMH leads to changes in expression of pulmonary RAS of fetal mice. The possible implications of these changes for the regulation of pulmonary vascular contractility in later life remain to be explored.

Original languageEnglish (US)
Pages (from-to)180-189
Number of pages10
JournalReproductive Sciences
Volume18
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • DNA methylation
  • Developmental origins
  • MicroRNA

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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