PMID- 9428419
OWN - NLM
STAT- MEDLINE
DCOM- 19980202
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 124
IP  - 23
DP  - 1997 Dec
TI  - Increased cell death in rat blastocysts exposed to maternal diabetes in utero and 
      to high glucose or tumor necrosis factor-alpha in vitro.
PG  - 4827-36
AB  - The morphogenetic function of the transient phase of cell death that occurs 
      during blastocyst maturation is not known but it is thought that its regulation 
      results from a delicate balance between survival and lethal signals in the 
      uterine milieu. In this paper, we show that blastocysts from diabetic rats have a 
      higher incidence of dead cells than control embryos. Differential lineage 
      staining indicated that increased nuclear fragmentation occurred mainly in the 
      inner cell mass. In addition, terminal transferase-mediated dUTP nick end 
      labeling (TUNEL) demonstrated an increase in the incidence of non-fragmented 
      DNA-damaged nuclei in these blastocysts. Analysis of the expression of clusterin, 
      a gene associated with apoptosis, by quantitative reverse 
      transcription-polymerase chain reaction detected an increase in the steady-state 
      level of its transcripts in blastocysts from diabetic rats. In situ hybridization 
      revealed that about half the cells identified as expressing clusterin mRNA 
      exhibited signs of nuclear fragmentation. In vitro experiments demonstrated that 
      high D-glucose increased nuclear fragmentation, TUNEL labeling and clusterin 
      transcription. Tumor necrosis factor-alpha (TNF-alpha), a cytokine whose 
      synthesis is up-regulated in the diabetic uterus, did not induce nuclear 
      fragmentation nor clusterin expression but increased the incidence of 
      TUNEL-positive nuclei. The data suggest that excessive cell death in the 
      blastocyst, most probably resulting from the overstimulation of a basal suicidal 
      program by such inducers as glucose and TNF-alpha, may be a contributing factor 
      of the early embryopathy associated with maternal diabetes.
FAU - Pampfer, S
AU  - Pampfer S
AD  - Physiology of Reproduction Research Unit (OBST 5330) University of Louvain 
      Medical School, Brussels, Belgium. pampfer@obst.ucl.ac.be
FAU - Vanderheyden, I
AU  - Vanderheyden I
FAU - McCracken, J E
AU  - McCracken JE
FAU - Vesela, J
AU  - Vesela J
FAU - De Hertogh, R
AU  - De Hertogh R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Clusterin)
RN  - 0 (Glycoproteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Blastocyst/*cytology/drug effects
MH  - Cell Death/drug effects
MH  - Cell Nucleus/ultrastructure
MH  - Clusterin
MH  - DNA Fragmentation
MH  - Female
MH  - Glucose/*pharmacology
MH  - Glycoproteins/genetics
MH  - Male
MH  - *Molecular Chaperones
MH  - Pregnancy
MH  - *Pregnancy in Diabetics
MH  - RNA, Messenger
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1998/01/15 00:00
MHDA- 1998/01/15 00:01
CRDT- 1998/01/15 00:00
PHST- 1998/01/15 00:00 [pubmed]
PHST- 1998/01/15 00:01 [medline]
PHST- 1998/01/15 00:00 [entrez]
AID - 10.1242/dev.124.23.4827 [doi]
PST - ppublish
SO  - Development. 1997 Dec;124(23):4827-36. doi: 10.1242/dev.124.23.4827.