PMID- 10508975
OWN - NLM
STAT- MEDLINE
DCOM- 19991105
LR  - 20161124
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 60
IP  - 4
DP  - 1999 Oct
TI  - Hypoxic microenvironment within an embryo induces apoptosis and is essential for 
      proper morphological development.
PG  - 215-25
AB  - Recent studies have suggested the importance of hypoxia-inducible transcription 
      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 development remain 
      unanswered. In this study, we directly demonstrate that regions of hypoxia, most 
      prominently the hindbrain, otic vesicle, and first branchial arch, exist in a 
      gestational day (GD) 11 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 cranial 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% oxygen during the same period were stunted in overall 
      growth, yet morphologically normal, and displayed prominent areas of apoptosis. 
      In this study, we propose that embryonic development, like tumor development, 
      requires two different 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 cues that drives normal embryonic development. The requirement for 
      hypoxia to activate apoptotic cell death is but one example of such interactions.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Chen, E Y
AU  - Chen EY
AD  - Mayer Cancer Biology Research Laboratory, Department of Radiation Oncology, 
      Stanford University School of Medicine, Stanford, California 94305-5468, USA.
FAU - Fujinaga, M
AU  - Fujinaga M
FAU - Giaccia, A J
AU  - Giaccia AJ
LA  - eng
GR  - CA09302/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Brain/drug effects/*embryology
MH  - Embryo, Mammalian/cytology/*physiology
MH  - Embryonic and Fetal Development/drug effects/*physiology
MH  - Female
MH  - *Hypoxia
MH  - Microcephaly/etiology
MH  - Morphogenesis/drug effects
MH  - Neural Tube Defects/etiology
MH  - Oxygen/pharmacology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1999/10/06 00:00
MHDA- 1999/10/06 00:01
CRDT- 1999/10/06 00:00
PHST- 1999/10/06 00:00 [pubmed]
PHST- 1999/10/06 00:01 [medline]
PHST- 1999/10/06 00:00 [entrez]
AID - 10.1002/(SICI)1096-9926(199910)60:4<215::AID-TERA6>3.0.CO;2-2 [pii]
AID - 10.1002/(SICI)1096-9926(199910)60:4<215::AID-TERA6>3.0.CO;2-2 [doi]
PST - ppublish
SO  - Teratology. 1999 Oct;60(4):215-25. doi: 
      10.1002/(SICI)1096-9926(199910)60:4<215::AID-TERA6>3.0.CO;2-2.