Profile of Apoptotic Marker Genes and Histopathology of the Placenta in Pregnancies with Pre-Eclampsia

Herlambang Herlambang, Rina Nofri Enis, Susan Tarawifa, Huntari Harahap, Anggelia Puspasari, Citra Maharani, Erny Kusdiyah

Abstract


Background: Pre-eclampsia (PE) is a hypertensive disorder in pregnancy and a significant cause of maternal and perinatal mortality and morbidity. Failure of spiral artery remodeling due to abnormal apoptosis, triggers disturbances in the mother and the baby’s growth. This study aimed to identify the profile of apoptotic marker genes and histopathological features of the placenta in pregnancies with pre-eclampsia.

Methods: This study had used case-control method. Samples were taken from normal pregnancies (n=25) and pregnant women with pre-eclampsia (n=25) using a purposive sampling method from several hospitals in Jambi. qRT-PCR was used to examine apoptotic gene expression from placental tissue and hematoxyline eosin staining to view the placenta’s microscopic appearance. The targeted genes were BCL2-associated X (BAX) and B-cell lymphoma 2 (BCL-2). Histopathological changes of the placenta observed were syncytial node, cytotrophoblast, villous edema, hypervascularization, fibrosis stroma, atherosis, infarction, and thrombosis.

Results: Relative BAX genes expression were increased once in placenta pre-eclampsia compared to controls, but not statistically significant (p-value>0.05). There was no difference between the decline of BCL-2 gene expression in pre-eclampsia placenta compared to the control (p-value >0.05). Histopathological changes in the placenta were syncytial node and cytotrophoblast (25 of 25), villous edema (19 of 25), hypervascularization (24 of 25), fibrosis stroma (22 of 25), atherosis (12 of 25), infarction (17 of 25), and thrombosis (24 of 25).

Conclusion: The expression of BAX genes in pre-eclampsia tends to increase compared to normal pregnancy, and the expression of BCL-2 decreases.  The histopathological features of pre-eclampsia pregnancy placenta are mostly syncytial nodes, cytotrophoblasts, stromal fibrosis, and thrombosis.


Keywords


BAX, BCL-2, histopathology placenta, pre-eclampsia

Full Text:

PDF

References


  1. WHO. Maternal mortality the sustainable development goals and the global strategy for women’s, children’s and adolescent’s health [Internet]. who.int. 2020 [cited 2022 October 12]. Available from: https://www.who.int/news-room/fact-sheets/detail/maternal-mortality.
  2. Dinas Kesehatan Provinsi Jambi. Profil kesehatan Provinsi Jambi tahun 2020. Jambi: Dinas Kesehatan Provinsi Jambi; 2021 [cited 2022 October 10]. Available from: https://dinkes.jambiprov.go.id/file/informasi_publik/MICAyMDIwLnBkZgMTY0MTI2NzkyOA_Wkt1641267928_XtLnBkZg.pdf
  3. Kasriatun K, Kartasurya MI, Nugraheni SA. Faktor risiko internal dan eksternal preeklampsia di Wilayah Kabupaten Pati Provinsi Jawa Tengah. J Manajemen Kesehatan Indonesia. 2019;7(1):30–8.
  4. Khalil G, Hameed A. Preeclampsia: pathophysiology and the maternal-fetal risk. J Hypertens Manag. 2017;3(1):024.
  5. Armaly Z, Jadaon JE, Jabbour A, Abassi ZA. Pre-eclampsia: novel mechanisms and potential therapeutic approaches. Front Physiol. 2018;9:973.
  6. Wibowo N, Irwinda R, Frisdiantiny E, Karkata MK, Mose JC, Chalid MT, et al. Pedoman nasional pelayanan kedokteran: diagnosis dan tata laksana pre-eklamsia. Jakarta: Perkumpulan Obstetri dan Ginekologi Indonesia; 2016.
  7. Surico D, Bordino V, Cantaluppi V, Mary D, Gentilli S, Oldani A, et al. Preeclampsia and intrauterine growth restriction: Role of human umbilical cord mesenchymal stem cells-trophoblast cross-talk. PLoS One. 2019;14(6):e0218437.
  8. Shields CA, McCalmon M, Ibrahim T, White DL, Williams JM, LaMarca B, et al. Placental ischemia-stimulated T-helper 17 cells induce preeclampsia-associated cytolytic natural killer cells during pregnancy. Am J Physiol Regul Integr Comp Physiol. 2018;315(2):R336–43.
  9. Escudero C, Bertoglia P, Hernadez M, Celis C, Gonzalez M, Aguayo C. et al. Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset pre-eclampsia. Purinergic Signal. 2013;9(2):215–26.
  10. Wu F, Tian F-J, Lin Y. Oxidative stress in placenta: health and diseases.. Biomed Res Int. 2015;2015: 293271.
  11. Arianto B, Hadiati DR, Nurdiati DS. Perbandingan rerata ekspresi Bcl-2 dan Bcl-Xl pada preeklamsia berat dan kehamilan normotensi. Jurnal Kesehatan Reproduksi. 2015;2(2):77–84.
  12. Payne B, Hoodbhoy Z. Risk factors and predictors of pre-eclampsia. In: Magee LA, von Dadelszen P, Stones W, Mathai M, editors. The FIGO textbook of pregnancy hypertension: an evidence-based guide to monitoring, prevention and management. London, UK: The Global of Library of Women’s Medicine; 2016. p. 75–101.
  13. Fox R, Kitt J, Leeson P, Aye CYL, Lewandowski AJ. Pre-eclampsia: risk factors, diagnosis, management, and the cardiovascular impact on the offspring. J Clin Med. 2019;8(10):1625.
  14. Mayrink J, Souza RT, Feitosa FE, Rocha Filho EA, Leite DF, Vettorazzi J, et al. Incidence and risk factors for Preeclampsia in a cohort of healthy nulliparous pregnant women: a nested case-control study. Sci Rep. 2019;9(1):9517.
  15. Prawirohardjo S. Ilmu kebidanan. 4th ed. Jakarta: PT. Bina Pustaka Sarwono Prawirohardjo. 2020.
  16. Sujatmiko T, Rumekti DR, Nurdiati DS. Perbandingan rerata ekspresi protein bax dan bak pada preeklampsia berat dan kehamilan normotensi. Jurnal Kesehatan Reproduksi. 2015;2(3):146–52.
  17. Liiv I, Haljasorg U, Kisand K, Maslovskaja J, Laan M, Peterson P. AIRE-induced apoptosis is associated with nuclear translocation of stress sensor protein GAPDH. Biochem Biophys Res Commun. 2012;423(1):32–7.
  18. Sermeus A, Michiels C. Reciprocal influence of the p53 and the hypoxic pathways. Cell Death Dis. 2011;2(5):e164.
  19. Zhang JY, Zhang F, Hong CQ, Giuliano AE, Cui XJ, Zhou GJ, et al. Critical protein GAPDH and its regulatory mechanisms in cancer cells. Cancer Biol Med. 2015;12(1):10–22.
  20. Ezeigwe CO, Okafor CI, Eleje GU, Udigwe GO, Anyiam DC. Placental peripartum pathologies in women with preeclampsia and eclampsia. Obstet Gynecol Int. 2018;2018:9462938.
  21. Herlambang H, Enis RN, Tarawifa S,, Ekaputri TW. Identification of apoptosis marker in preeclampsia: a pre-eliminary study of P53 gene expression in human placenta. In: Budu, Nurkristina T, Findyartini A, editors. GDIC 2020. Proceeding of The 3rd Green Development International Conference; 2020 October 2-3; Jambi, Indonesia. Jambi: Atlantis Press. 2021. p. 209–213.
  22. Toro AR, Maymó JL, Ibarbalz FM, Pérez A, Maskin B, Faletti AG, et al. Leptin is an anti-apoptotic effector in placental cells involving p53 downregulation. PLoS One. 2014;9(6):e99187.
  23. Wei D, Wu Q, Shi H. Apoptosis and p53 expression in the placental villi of females with unexplained recurrent spontaneous abortion. Exp Ther Med. 2014;7(1):191–4.
  24. Zhai D, Chin K, Wang M, Liu F. Disruption of the nuclear p53-GAPDH complex protects against ischemia-induced neuronal damage. Mol Brain. 2014;7:20.
  25. Schoots MH, Gordijn SJ, Scherjon SA, van Goor H, Hillebrands JL. Oxidative stress in placental pathology. Placenta. 2018;69:153–61.
  26. Gore CR, Pandey A, Shetty A, Rao R, Paranjape S. A study on histopathological changes in placenta in pre-eclampsia/eclampsia: a case-control study in tertiary care centre, western India. Indian J Pathol Oncol. 2018;5(3):385–90.
  27. Donthi D, Malik P, Mohamed A, Kousar A, Subramanian RA, Manikyam UK. An objective histopathological scoring system for placental pathology in pre-Eclampsia and eclampsia. Cureus. 2020;12(10):e11104.
  28. Ranjan DS, Gyanaranjan N, Bhusan MB, Sreepreeti C. Histopathological study of placenta in pregnancy with hypertension in western Odisha. IOSR-JDMS. 2017;16(6):100–4.
  29. Klatt EC, Kumar V. Robbins and Cotran: review of pathology. 4th Ed. Philadelphia: Elsevier Saunders; 2014.




DOI: https://doi.org/10.15850/amj.v10n2.3088

Article Metrics

Abstract view : 464 times
PDF - 226 times


 This Journal indexed by

                  

          

 

Creative Commons License
AMJ is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

 


View My Stats