Accession Number : AD1046737


Title :   Novel Models to Study Effect of High-Altitude Hypoxic Exposure and Placental Insufficency on Fetal Oxygen Metabolism and Congenital Heart Defects


Descriptive Note : Technical Report,30 Sep 2015,29 Sep 2016


Corporate Author : University of Maryland School of Medicine Baltimore United States


Personal Author(s) : Fisher,Steven A


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1046737.pdf


Report Date : 01 Oct 2016


Pagination or Media Count : 28


Abstract : The goals are 1) to define vulnerability of the embryonic heart to oxygen (O2) deprivation 2) to determine if placental insufficiency induced by knock-out of HIF1a in the mother (MATcKO) increases this vulnerability and how. We used the ODDLuc hypoxia reporter as a sensitive read-out of tissue oxygenation. We have found that even moderate acute reductions in maternal inspired O2 (to 12%, room air is 21%) induce a hypoxic response in the embryonic heart at mid-gestation. During the remainder of the funding period we will be testing milder hypoxic conditions (to 18%) at different stages of development. For the 2nd aim we have found that MATcKO HIF1a causes a number of defects in the developing placenta, including reduced invasion by uterine natural killer cells (uNK) and conceptus-derived trophoblast cells. The placental defects do not alter basal O2 delivery to the embryo but make it more vulnerable to O2 deprivation. Some embryos are non-viable at E15 with abnormal hearts but do not model human CHD. Further experiments will examine stagedependent effects of O2 deprivation in this model. The developing fetal heart is vulnerable to even mild O2 deprivation at mid-gestation, and this may be compounded by placental defects.


Descriptors :   Hypoxia , Placenta , Congenital Heart Defects , EMBRYOS


Subject Categories : Medicine and Medical Research
      Anatomy and Physiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE