Sandra Zekić Tomaš
Name: prof. dr. sc. SANDRA ZEKIĆ TOMAŠ dr. med.
Thesis title: "EXPRESSION AND ROLE OF FAS LIGAND IN ACTIVATION OF EXTRINSIC APOPTOTIC PATHWAY IN THE TROPHOBLAST OF PLACENTAS FROM PREECLAMPSIA-COMPLICATED PREGNANCIES"
Mentor: prof. dr. sc. KUZMIĆ PRUSAC IVANA
Qualifying research publications:
Tomas SZ, Prusac IK, Roje D, Tadin I. Trophoblast apoptosis in placentas from pregnancies complicated by preeclampsia. Gynecol Obstet Invest.2011;71(4):250-5.
IF (JCR 2011) 1.276
Prusac IK, Zekic Tomas S, Roje D. Apoptosis, proliferation and Fasligand expression in placental trophoblast from pregnancies complicated by HELLP syndrome or pre-eclampsia. Acta Obstet Gynecol Scand.
2011;90(10):1157-63.
IF (JCR 2011) 1.771
Summary:
EXPRESSION AND ROLE OF FAS LIGAND IN ACTIVATION OF EXTRINSIC APOPTOTIC PATHWAY IN PLACENTAL TROPHOBLAST FROM PREGNANCIES COMPLICATED WITH PREECLAMPSIA
Objective: To investigate FasL expression and its role in apoptosis of placental trophoblast, to determine the apoptotic activity of placental trophoblast separately for CTB, STB, total villous trophoblast and trophoblast of syncytial knots, in placentas from PE pregnancies and normal pregnancies, and to compare them. To investigate the expression of antiapoptotic Bcl-2 factor and proliferation Ki-67 factor in trophoblast of placentas from PE and normal pregnancies and to determine their relation to the expression of FasL and apoptotic activity. To investigate the histopathologycal characteristics of studied placentas.
Material and methods: The study enrolled data and placentas from 25 singleton third trimester PE pregnancies, and the same number of placentas from normal term pregnancies. Clinical diagnosis of PE was made by following criteria: arterial hypertension in previously normotensive patient and proteinuria. Exclusion criteria were: arterial hypertension, cardiovascular and renal diseases that existed prior to pregnancy, diagnosis of HELLP syndrome and signs of impaired coagulation system. Apoptotic and proliferation activity was determined with M30 antibody and antigen Ki-67. Expression of FasL and Bcl-2 factor was determined by HSCORE method. From the placental histopathology findings, following was noted: diameter, length and cord insertion, circulatory disorders, ramification, maturity and villus vascularization; development of syncytiocapillary membranes, and characteristics of syncytial knots.
Results: PE placental trophoblast has significantly higher apoptotic index of CTB-a (P=0,002), STB (P<0,001), total villous trophoblast (P<0,001) and trophoblast of syncytial knots (P<0,001) compared to the control placental group. There is a significant difference between the examined apoptotic indexes within the group of PE placentas (P <0.001); the apoptotic index is lowest in the CTB, higher in the STB and total villous trophoblast, and the highest in the trophoblast of syncytial knots. CTB proliferation activity is significantly positively correlated with the apoptotic activity of CTB in the control group (P = 0,045). FasL expression is significantly lower in villous trophoblast (P<0,001) and trophoblast of syncytial knots (P<0,001) in PE placentas compared to the control group. Expression of Bcl-2 factors is significantly higher in the villous trophoblast (P<0,001) and trophoblast of syncytial knots (P<0,001) in PE placentas compared to control group. Expression of FasL and Bcl-2 factors is significantly positively correlated in the control placental group in the villous trophoblast (P = 0,001) and trophoblast of syncytial knots (P = 0,001). CTB proliferation activity and FasL expression in total villous trophoblast are in positive and significant correlation in the control group (P = 0.007). PE placentas have significantly smaller number of placental villi (P<0,001) and the average number of nuclei in the syncytial knots (P<0,001), while the number of syncytial knots (P<0,001), the ratio of the number of syncytial knots and placental villi (P<0,001), total number of nuclei in the syncytial knots (P<0,001), and average surface of syncytial knots (P= 0.002) are significantly higher compared to the control group.
Conclusion: increased trophoblast apoptotic activity in the placentas from PE indicates fast „trophoblast turnover", which leads to the formation of syncytial knots, qualitatively different from those in the placentas of normal pregnancies. Reduced expression of FasL in the placentas from PE is unable to cause increased apoptosis, and to prevent the release of aberrant syncytial knots in the mother's circulation. The loss of correlation between FasL and Bcl-2 factor in placentas from PE is another evidence of impaired apoptosis. The increased expression of Bcl-2 factor in PE placentas compared to the control group is a response to increased apoptotic activity. Correlation between FasL and proliferation activity is preserve in the control group, but lost in the study group, indicating multiple roles of FasL, but also on the other hand supporting the fact of its deficiency in PE.
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