Altered gene expression of caspase-10, death receptor-3 and IGFBP-3 in preeclamptic placentas.

Enhanced apoptosis has been observed in the placentas of women with preeclampsia, but few studies have examined changes at the molecular level. This study was designed to detect genes specifically expressed in full-term preeclamptic placentas. Tissue samples were collected immediately after cesarean delivery from 11 normal and 8 preeclamptic placentas at 35-40 weeks of gestation. Total RNAs were extracted and hybridized to a cDNA microarray. Results were confirmed by reverse-transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Hematoxylin and eosin and TUNEL staining were also performed to confirm apoptosis in preeclamptic placentas. Among 205 genes, three were up- or down-regulated in preeclamptic placentas. The expression of caspase-10 and death receptor 3 (DR-3) was significantly increased, whereas insulin-like growth factor binding protein-3 (IGFBP-3) was strongly down-regulated. RT-PCR analysis and Western blotting confirmed these effects. Immunohistochemical analysis showed that the DR-3, caspase-10 and IGFBP-3 proteins were localized in the syncytial membrane. Apoptosis in the trophoblast was also increased in term placentas from women with pregnancies complicated by preeclampsia. These results suggest that caspase-10, DR-3 and IGFBP-3 are involved in apoptosis in the preeclamptic placenta.