Troglitazone attenuates hypoxia-induced injury in cultured term human trophoblasts.
OBJECTIVE
The purpose of this study was to test the hypothesis that the thiazolidinedione troglitazone, a peroxisome proliferator activated receptor-gamma ligand, attenuates hypoxia-induced trophoblast injury.


METHODS
Cytotrophoblasts from 4 term human placentas were cultured in the presence or absence of 10 mumol/L troglitazone in either 20% oxygen (standard conditions) or 1% oxygen (hypoxic conditions) for variable periods before cell harvest. Medium beta-human chorionic gonadotropin and human placental lactogen were analyzed by enzyme-linked immunosorbent assay. Apoptosis was quantified by cytokeratin-18 cleavage products staining; p53 expression was examined by Western blot analysis.


RESULTS
beta-human chorionic gonadotropin and human placental lactogen levels were >/=2-fold higher in troglitazone-exposed cells at 16 hours of hypoxia, compared with vehicle control cells ( P <.05). The apoptotic index was reduced by >/=30% ( P <.001), and the expression of p53 was 2-fold lower ( P <.02) in troglitazone-exposed cells under hypoxia for </=16 hours but not different after >24 hours of low oxygen.


CONCLUSIONS
Troglitazone attenuates the influence of acute hypoxia on cultured term human trophoblasts.
Elchalal
Uriel
U
Departments of Obstetrics and Gynecology and Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO, USA.
Humphrey
Rachel G
RG
Smith
Steven D
SD
Hu
Chaobin
C
Sadovsky
Yoel
Y
Nelson
D Michael
DM
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000098:blood supply / Q000166:cytology; D011247:Pregnancy; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D000077288:Troglitazone; D014327:Trophoblasts / Q000187:drug effects* / Q000502:physiology
D002839:Chromans; D045162:Thiazolidinediones; D000077288:Troglitazone