University of Maryland School of Medicine Baltimore United States
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.