Submitted on April 6, 2005
Accepted on September 26, 2005
Preserved placental oxygenation and development during severe systemic hypoxia
Leonhard Schaffer1*, Johannes Vogel2, Christian Breymann3, Max Gassmann2, and Hugo H Marti4
1 Department of Obstetrics, Division of Perinatal Physiology, University Hospital of Zurich, Zurich, Switzerland; Institute of Physiology, University of Zurich, Zurich, Switzerland
2 Veterinary Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland
3 Department of Obstetrics, Division of Perinatal Physiology, University Hospital of Zurich, Zurich, Switzerland
4 Institute of Physiology, University of Zurich, Zurich, Switzerland; Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany
* To whom correspondence should be addressed. E-mail: leonhard.schaeffer{at}usz.ch.
Local tissue oxygenation profoundly influences placental development. To elucidate the impact of hypoxia on cellular and molecular adaptation in vivo, pregnant mice at embryonic day 7.5 - 11.5 were exposed to reduced environmental oxygen (6-7% O2) for various periods of time. HIF-1
mRNA was highly expressed in the placenta while HIF-2 was predominantly found in the decidua indicating that HIF-1 is a relevant oxygen-dependent factor involved in placental development. During severe hypoxia, HIF-1 protein was strongly induced in the periphery, however, not in the labyrinth layer of the placenta. Accordingly, no indication for tissue hypoxia in this central area was detected using EF-5 staining and VEGF expression as hypoxic markers. The absence of significant tissue hypoxia was reflected by preserved placental architecture and trophoblast differentiation. In the search for mechanisms preventing local hypoxia we found upregulation of endothelial NO synthase (eNOS) expression in the labyrinth layer. Inhibition of NOS activity by L-NAME application resulted in ubiquitous placental tissue hypoxia. Our results show that even during severe systemic hypoxia placental oxygenation is preserved and imply that NOS-mediated mechanisms are involved to protect the placenta from maternal hypoxia.
