The Dynamics of Cullin-1 Expression in Preeclamptic Placenta and its Association with Pregnancy Termination Time

  • Makbruri Makbruri Biomedical Science Program, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Department of Biology, Faculty of Medicine and Health Science, Bengkulu University, Bengkulu, Indonesia
  • Isabella Kurnia Liem Department of Anatomy, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
  • Ahmad Aulia Jusuf Department of Histology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
  • Tantri Hellyanti Department of Anatomical Pathology, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Keywords: Cullin-1, placenta, preeclampsia, pregnancy


BACKGROUND: Preeclampsia is a systemic syndrome occurring in 3–5% of pregnancies, caused by disorders of cellular factors resulting in the disruption of trophoblast differentiation and invasion which is important for the placental development and maintaining pregnancy. Cullin-1 is a protein that plays a role in the process of maintaining pregnancy, development, and trophoblast invasion in the placenta. Until now, there have been no studies linking the expression of cullin-1 in preeclamptic patients with the timing of pregnancy termination.

AIM: This study analyzed cullin-1 expression in preeclamptic patients and their relationship to the timing of pregnancy termination was carried out.

METHODS: Placental samples were taken from preeclampsia patients consisting of three gestational age groups, then immunohistochemical staining was performed to see the dynamics of expression and distribution in each age group of pregnancy and to find out their relationship with the timing of pregnancy termination.

RESULTS: Cullin-1 was expressed in syncytiotrophoblasts and cytotrophoblasts. The lowest cullin-1 level was obtained in the very preterm age group, and the highest was found in the moderate preterm gestational age group. There was a significant difference between cullin-1 optical density (OD) expression and termination time of pregnancy, and there was a significant difference (OD) in cullin-1 preeclamptic patients with very preterm gestational age with moderate preterm gestational age.

CONCLUSION: Cullin-1 was expressed both in syncytiotrophoblasts and cytotrophoblasts and was associated with the timing of pregnancy termination.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Högberg U. The world health report 2005: Make every mother and child count including Africans. Scand J Public Health. 2005;33(6):409-11. PMid:16332605

Ray JG, Vermeulen MJ, Schull MJ, Redelmeier DA. Cardiovascular health after maternal placental syndromes (CHAMPS): Population-based retrospective cohort study. Lancet. 2005;366(9499):1797- 803. PMid:16298217

ACOG Committee on Practice Bulletins--Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol. 2002;99(1):159-67. https://doi. org/10.1016/s0029-7844(01)01747-1 PMid:16175681

Young BC, Levine RJ, Karumanchi SA. Pathogenesis of preeclampsia. Annu Rev Pathol. 2010;5:173-92. PMid:20078220

Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649-58. PMid:12618519

Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642-9. https://doi. org/10.1038/nm1429 PMid:16751767

Reister F, Frank HG, Kingdom JC, Heyl W, Kaufmann P, Rath W, et al. Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women. Lab Invest. 2001;81(8):1143-52. labinvest.3780326 PMid:11502865

Malhotra SS, Banerjee PY, Gupta SK. Regulation of throphoblast differentiation during embryo implantation and placentation: Implications in pegnancy complications. J Reprod Health Med. 2016;2 Suppl 2:S26-36.

Ji L, Brkić J, Liu M, Fu G, Peng C, Wang YL. Placental trofoblas cell differentiation: Physiological regulation and pathological relevance to preeclampsia. Mol Aspects Med. 2013;34(5):981- 1023. PMid:23276825

Zhiang Q, Yu S, Huang X, Tan Y, Zhu C, Wang YL, et al. New insights into the function of cullin 3 in trophoblast invasion and migration. Reproduction. 2015;150(2):139-49. https://doi. org/10.1530/REP-15-0126 PMid:26021998

Singer JD, Gurian-West M, Clurman B, Roberts JM. Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. Genes Dev. 1999;13(18):2375-87. https://doi. org/10.1101/gad.13.18.2375 PMid:10500095

Nakayama KI, Nakayama K. Ubiquitin ligases; cell-cycle control and cancer. Nat Rev Cancer. 2006;6(5):369-81. https://doi. org/10.1038/nrc1881 PMid:16633365

Petroski MD, Deshaises RJ. Function and regulation of cullin- RING ubiquitin ligases. Nat Rev Mol Cell Biol. 2005;6(1):9-20. PMid:15688063

Lee J, Zhou P. Cullins and cancer. Genes Cancer. 2010;1(7):690-9. PMid:21127736

Zheng N, Schulmann BA, Song L, Miller JJ, Jeffrey PD, Wang P, et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002;416(6882):703-9. https://doi. org/10.1038/416703a PMid:11961546

Fan Y, Zhu YS, Mei PJ, Sun SG, Zhang H, Chen CF, et al. Cullin-1 regulates proliferation, migration, and invasion of glioma cells. Med Oncol. 2014;31(10):227. PMid:25201578

Carrano AC, Eytan E, Hersko A, Pagano M. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol. 1999;1(4):193-9. PMid:10559916

Moro A, Savio AS, Morera Y, Perea SE. P27: Regulation and function of a cell cycle key regulator. Biotecnol Apl. 2001;18(4):193-202.

Knofler M. Critical growth factors and signalling pathways controlling human trophoblast invasion. Int J Dev Biol. 2010;54(2-3):269-80. PMid:19876833

Bischof P, Meisser A, Campana A. Paracrine and autocrine regulators of trophoblast invasion a review. Placenta. 2000;21 Suppl A:S55-60. PMid:10831123

Sadler TW. Langman’s Medical Embriology. 11th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005. p. 31-51.

Gude NM, Roberts CT, Kalionis B, King RG. Growth and function of the normal human placenta. Thromb Res. 2004;114(5-6):397- 407. PMid:15507270

Kliman HJ. From Trophoblast to Human Placenta (from The Encyclopedia of Reproduction; 2006. Available from: Placenta-(from-The-of-Kliman/95e7848513234d310a0dbda d54e5175aaa09ce53#paper-header. plac.2001.0747. [Last accessed on 2019 Sep 01].

How to Cite
Makbruri M, Liem IK, Jusuf AA, Hellyanti T. The Dynamics of Cullin-1 Expression in Preeclamptic Placenta and its Association with Pregnancy Termination Time. Open Access Maced J Med Sci [Internet]. 2020May22 [cited 2020Oct.31];8(B):210-5. Available from:
Gynecology and Obstetrics