Diah Rumekti Hadiati
* Corresponding Author Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia Indonesia
Arsi Palupi Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
Mohammad Hakimi Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
Sofia Mubarika Haryana Department of Histology and Cell Biology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
Diah Rumekti Hadiati(1*), Arsi Palupi(2), Mohammad Hakimi(3), Sofia Mubarika Haryana(4)
(1) Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (2) Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (3) Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (4) Department of Histology and Cell Biology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (*) Corresponding Author
Abstract
Preeclampsia is one of the main causes of maternal and perinatal mortality and morbidity. The pathogenesis of preeclampsia remains unclear until now. It is believed that regulation of apoptosis in trophoblast cells plays an important role in the pathophysiology of preeclampsia. Failure of spiral arteries remodeling will eventually lead to placental hypoxia lead to excessive trophoblast apoptosis. The molecular mechanism of apoptosis is very complicated involving many signaling molecules included Bcl-2 proteins. The Bcl- 2 protein group consists of proapoptosis proteins (Bax) and apoptosis inhibitor proteins (Bcl-2 and Bcl-xL). The aimed of this stuty was to compare the expression of Bcl-xL protein in placental trophoblast cells of pregnancy complicated by severe preeclampsia with that normotensive pregnancy. This study was an observational study with cross sectional design involving 43 pregnancy patients with severe preeclampsia and 38 normotensive pregnancy who treated in Dr. Sardjito General Hospital, Yogyakarta from October 2011 until March 2012. Placenta samples were obtained from all subjects for Bcl-xL protein expression analysis using immunohistochemistry technique. Data were analyzed using independent t-test, chi-square test, and logistic regression. A p value <0.05 was considered significant. Significant difference in Bcl-xL protein expression in trophoblast cells of pregnancy complicated by severe preeclampsia (1.29 ± 0.12) compared to that normotensive pregnancy (1.71 ± 0.14) was reported (p = 0.00). In addition, logistic regression test showed that diagnosis of severe preeclampsia had a statistically significant role in Bcl-xL protein expression (p= 0.000). In conclusion, the expression of Bcl-xL protein is lower in pregnancy complicated by severe preeclampsia compared to normotensive pregnancy.
Keywords
trophoblast; severe preeclampsia; Bcl-xL protein; apoptosis
Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010; 376(9741):631-44. http://dx.doi.org10.1016/S0140-6736(10)60279-62.
Levy R. The role of apoptosis in preeclampsia. Isr Med Assoc J 2005; 7(3):178-81.
Straszewski-Chavez SL, Abrahams VM, Mor G. The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr Rev 2005; 26(7):877-97. http://dx.doi.org/10.1210/er.2005-00034.
Heazell AE, Buttle HR, Baker PN, Crocker IP. Altered expression of regulators of caspase activity within trophoblast of normal pregnancies and pregnancies complicated by preeclampsia. Reprod Sci 2008; 15(10):1034-43. http://dx.doi.org/10.1177/1933719108322438
Jasovic-Siveska E, Jasovic V, Stoilova S. Previous pregnancy history, parity, maternal age and risk of pregnancy induced hypertension, Bratisl Lek Listy 2011; 112(4):188-191.
Sharp AN, Heazell AEP, Baczyk D, Dunk CE, Lacey HA, Jones CJP, et al. Preeclampsia is associated with alterations in the p53 pathway in villous trophoblast. PLoS ONE 2014; 9(1):e87621. http://dx.doi.org/10.1371/journal.pone.0087621
Zhang Z, Yang X, Zhang L, Duan Z, Jia L, Wang P, et al. Decreased expression and activation of stat3 in severe preeclampsia. J Mol His 2014; 46(2):205-219. http://dx.doi.org/10.1007/s10735-015-9613-8
Macdonald-Wallis C, Tilling K, Fraser A, Nelson SM, Lawlor DA. Established preeclampsia risk factors are ralted to patterns of blood pressure change in normal term pregnancy: findings from Avon Longitudinal Study of Parents and Children, J Hypertens 2011; 29(9):1703-11. https://doi.org/10.1097/HJH.0b013e328349eec6
Lamminpaa R, Vehviläinen-Julkunen K, Gissler M, Heinonen S. Preeclampsia complicated by advance maternal age: a registry-based study on primiparous women in Finland 1997-2008, BMC Pregnancy Childbirth 2012; 12:47. https://doi.org/10.1186/1471-2393-12-47
Allaire AD, Ballenger KA, Wells SR, McMahon MJ, Lessey BA. Placental apoptosis in preeclampsia. Obstet Gynecol 2000; 96(2):271-6. http://dx.doi.org/10.1097/00006250-200008000-00022
Shu C, Liu Z, Cui L, Wei C, Wang S, Tang JJ, et al. Protein profiling of preeclampsia placental tissues. PLoS ONE 2014; 9(11):e112890. http://dx.doi.org/10.1371/journal.pone.0112890
Hung TH, Chen SF, Liou JD, Hsu JJ, Li MJ, Yeh YL, et al. Bax, bak and mitochondrial oxidants are involved in hypoxia-reoxygenation-induced apoptosis in human placenta. Placenta 2008; 29(7):565-83. http://dx.doi.org/10.1016/j.placenta.2008.03.005
Whitehead CL, Walker SP, Lappas M, Tong S. Circulating RNA coding genes regulating apoptosis in maternal blood in severe early onset fetal growth restriction and pre-eclampsia. J Perinatol 2013; 33:600-4. http://dx.doi.org/10.1038/jp.2013.16
Kavathia N, Jain A, Walston J, Beamer BA, Fedarko NS. Serum markers of apoptosis decrease with age and cancer stage. Aging 2009; l(7):652-63. http://dx.doi: 10.18632/aging.100069
Smith SC, Baker PN, Symonds EM. Placental apoptosis in normal human pregnancy. Am J Obstet Gynecol 1997; 177(1):57-65.
16.Kim PKM, Zamora R, Petrosko P, Billiar T. The regulatory role of nitric oxide in apoptosis. Int Immunopharmacol 2001; 1(8):1421-41. http://dx.doi.org/10.1016/S1567-5769(01)00088-1
Kaufmann P, Black S, Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod 2003; 69(1):1-7. http://dx.doi.org/10.1177/1933719108322438