Ey. Chen et al., Hypoxic microenvironment within an embryo induces apoptosis and is essential for proper morphological development, TERATOLOGY, 60(4), 1999, pp. 215-225
Recent studies have suggested the importance of hypoxia-inducible transcrip
tion factors in development, yet the questions of whether hypoxia actually
exists in a developing embryo in vivo and, if so, what role it plays in dev
elopment remain unanswered. In this study, we directly demonstrate that reg
ions of hypoxia, most prominently the hindbrain, otic vesicle, and first br
anchial arch, exist in a gestational day (GD) II rat embryo grown in utero.
We also show that varying the oxygen environment of an embryo affects its
morphological development. Rat embryos which were grown at 45% oxygen from
GD 9-11 showed gross morphological abnormalities, including defective crani
al neural tube closure, incomplete otic vesicle invagination, and abnormal
somite formation and embryo turning. These embryos, in addition, exhibited
reduced cell death. On the other hand, embryos which were grown at 5% oxyge
n during the same period were stunted in overall growth, yet morphologicall
y normal, and displayed prominent areas of apoptosis. In this study, we pro
pose that embryonic development, like tumor development, requires two diffe
rent but interactive sets of signals. One set exists in the genetic program
for development; the other set arises from changes in the microenvironment
of the embryo. Therefore, it is the interplay between these two sets of cu
es that drives normal embryonic development. The requirement for hypoxia to
activate apoptotic cell death is but one example of such interactions. Ter
atology 60:215-225, 1999. (C) 1999 Wiley-Liss, Inc.