Study On Placental Apoptosis And Expression Of Its Related Proteins In Severe Pregnancy Induced Hypertension Syndrome

Pregnancy induced hypertension syndrome is a pregnancy-specific disease of reduced organ perfusion secondary to vasospasm and endothelial activation. It affects 7-13% of all pregnancies, and severe pregnancy induced hypertension syndrome (SPIH) is a major cause of maternal and fetal mortality. But its etiology remains unknown.Apoptosis differs from necrosis in that the former is an active form of cell death dependent on the internal machinery of the cell. The molecular mechanisms of apoptosis in humans are complex. Those include immune-mediated extracellular ligands and receptors such as the Fas ligand and Fas receptor, and endogenous death signals such as the Bcl-2 family of genes, which converge to activate a central executioner, the caspase cascade. And heat shock protein 70 (HSP70) plays a protective role and increases resistance to apoptosis.Studies on human placenta! apoptosis in normal and abnormal pregnancies have been continuously growing. These observation can imply that apoptosis may be a normal placental aging process. Apoptosis has been described in placentas of normal human pregnancies and is increased in pregnancies complicated by IUGR, etc. And apoptosis may also has an important role in the placentas of SPIH. This study will be helpful in further understanding the etiology of PEH.AIM The objective of this study was to determine whether there was an increase in placental apoptosis in pregnancies complicated by SPIH compared with placentas from normal pregnancy. To study the relationship between apoptosis and differential expression of Bax/Bcl-2, Fas/FasL, Cleaved Caspase-3 and HSP70 in placentas of SPIH. To explore the pathogenesis of PIH in placental apoptosis.METHODS Placental samples were obtained from 30 uncomplicated third-trimester pregnancies and from 30 cases of SPIH. We used terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining (TUNEL), light microscopy, electron microscopy to identify and quantify apoptosis. Expression of Fas, Fas ligand, Bcl-2, Bax, Cleaved Caspase-3 and HSP70 was detected by immunohistochemical staining . The expression of HSP70 protein was assessed by Western blot. RESULTS (1) Apoptosis has been conclusively demonstrated within human third-trimester placental tissue. Medians and interquartile ranges of SPIH group was 0.36 % ( 0.20%~0.46% ) ; and the normal control was 0.15% (0.09%~0.21%) . The incidence of apoptosis was higher in placentas of SPIH (P<0.05); (2) The positive rates of HSP70 were 100% in SPIH group and93% in control, but the intensity of staining was significantly different between these two groups (P<0.01). In comparison to normal control, the expression of HSP70 increased in placentas of SPEH group; (3) Bax, Fas and Cleaved Caspase-3 expression were also significantly greater in the villus trophoblast among the study group compared with controls. There was no difference in the expression of FasL, and Bcl-2 between two groups.CONCLUSION (1) Increased placental apoptosis and altered expression of Fas/FasL, Bcl-2/Bax and Cleaved Caspase-3 in trophoblast are simultaneous. It might influence pathogenesis of PIH. (2) Expression of HSP70 does not increase resistance to placental apoptosis in SPIH, and it may play a protective role in the pathophysiologic mechanisms of PIH. (3) For the relationship between placental apoptosis and the pathogenesis of PIH, we propose that the process, trophoblast normally sheds STBM (Syncytio- trophoblast microfragments) into maternal circulation, depends on apoptosis. PIH occurs when the burden of STBM is abnormally high.