PMID- 17392498
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20190508
IS  - 0006-3363 (Print)
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 77
IP  - 1
DP  - 2007 Jul
TI  - Epidermal growth factor-like growth factors prevent apoptosis of alcohol-exposed 
      human placental cytotrophoblast cells.
PG  - 53-60
AB  - Maternal alcohol abuse during pregnancy can produce an array of birth defects 
      comprising fetal alcohol syndrome. A hallmark of fetal alcohol syndrome is 
      intrauterine growth retardation, which is associated with elevated apoptosis of 
      placental cytotrophoblast cells. Using a human first trimester cytotrophoblast 
      cell line, we examined the relationship between exposure to ethanol and 
      cytotrophoblast survival, as well as the ameliorating effects of epidermal growth 
      factor (EGF)-like growth factors produced by human cytotrophoblast cells. After 
      exposure to 0-100 mM ethanol, cell death was quantified by the TUNEL method, and 
      expression of the nuclear proliferation marker, Ki67, was measured by 
      immunohistochemistry. The mode of cell death was determined by assessing annexin 
      V binding, caspase 3 activation, pyknotic nuclear morphology, reduction of TUNEL 
      by caspase inhibition, and cellular release of lactate dehydrogenase. Ethanol 
      significantly reduced proliferation and increased cell death approximately 
      2.5-fold through the apoptotic pathway within 1-2 h of exposure to 50 mM alcohol. 
      Exposure to 25-50 mM ethanol significantly increased transforming growth factor 
      alpha (TGFA) and heparin-binding EGF-like growth factor (HBEGF), but not EGF or 
      amphiregulin (AREG). When cytotrophoblasts were exposed concurrently to 100 mM 
      ethanol and 1 nM HBEGF or TGFA, the increase in apoptosis was prevented, while 
      EGF ameliorated at 10 nM and AREG was weakly effective. HBEGF survival-promoting 
      activity required ligation of either of its cognate receptors, HER1 or HER4. 
      These findings reveal the potential for ethanol to rapidly induce cytotrophoblast 
      apoptosis. However, survival factor induction could provide cytotrophoblasts with 
      an endogenous cytoprotective mechanism.
FAU - Wolff, Garen S
AU  - Wolff GS
AD  - C.S. Mott Center for Human Growth and Development, Department of Obstetrics & 
      Gynecology, Wayne State University School of Medicine, Detroit, Michigan 48201, 
      USA.
FAU - Chiang, Po Jen
AU  - Chiang PJ
FAU - Smith, Susan M
AU  - Smith SM
FAU - Romero, Roberto
AU  - Romero R
FAU - Armant, D Randall
AU  - Armant DR
LA  - eng
GR  - R01 AA011085/AA/NIAAA NIH HHS/United States
GR  - R01 AA011085-10/AA/NIAAA NIH HHS/United States
GR  - AA12057/AA/NIAAA NIH HHS/United States
GR  - Intramural NIH HHS/United States
GR  - AA11085/AA/NIAAA NIH HHS/United States
GR  - R29 AA011085/AA/NIAAA NIH HHS/United States
GR  - R37 AA011085/AA/NIAAA NIH HHS/United States
GR  - R01 AA012057-04/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070328
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Caspase Inhibitors)
RN  - 3K9958V90M (Ethanol)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/genetics/metabolism
MH  - Caspase Inhibitors
MH  - Cell Line
MH  - Cell Proliferation
MH  - Dose-Response Relationship, Drug
MH  - Epidermal Growth Factor/metabolism/*pharmacology
MH  - Ethanol/*pharmacology
MH  - Humans
MH  - Trophoblasts/*cytology/*drug effects/metabolism
MH  - Up-Regulation
PMC - PMC1950777
MID - NIHMS25018
EDAT- 2007/03/30 09:00
MHDA- 2007/09/26 09:00
PMCR- 2007/08/23
CRDT- 2007/03/30 09:00
PHST- 2007/03/30 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/03/30 09:00 [entrez]
PHST- 2007/08/23 00:00 [pmc-release]
AID - biolreprod.106.057984 [pii]
AID - 10.1095/biolreprod.106.057984 [doi]
PST - ppublish
SO  - Biol Reprod. 2007 Jul;77(1):53-60. doi: 10.1095/biolreprod.106.057984. Epub 2007 
      Mar 28.