Comparative analysis of plasma betatrophin levels with placental dysfunction in preeclamptic pregnancies: A histopathological and biochemical study
DOI:
https://doi.org/10.55629/pakjpathol.v36i2.903Abstract
Objective: This study compared plasma betatrophin levels and placental morphological and histopathological changes between preeclamptic and normotensive pregnancies.
Material and Methods: This cross-sectional study included 90 pregnant women recruited at LUMHS Jamshoro, equally divided into preeclamptic and normotensive groups. Researchers assessed four gross placental parameters: weight, volume, thickness, and number of cotyledons. Histological evaluation focused on identifying syncytial knots, cytotrophoblast proliferation, hypovascular villi, and villous necrosis. Plasma betatrophin levels were measured using a sandwich ELISA method. Data were analyzed using SPSS v22, with statistical significance set at p < 0.05.
Results: Histopathological and gross examination revealed that preeclamptic placentas had significantly lower weight, thickness, and volume, and demonstrated more frequent pathological changes (p < 0.005). Syncytial knots, cytotrophoblast proliferation, and villous necrosis were notably more common among preeclamptic patients (p < 0.01). Mean plasma betatrophin levels were significantly higher in women with preeclampsia (1.71 ± 0.06 µg/L) than in normotensive controls (1.66 ± 0.10 µg/L; p = 0.008), correlating with the extent of placental abnormalities.
Conclusion: Women with preeclampsia exhibited higher plasma betatrophin levels along with significant placental structural and histological abnormalities compared to normotensive controls.
Keywords: ANGPTL8, Betatrophin, Histopathology, Placental dysfunction, Preeclampsia
References
Tesfa E, Nibret E, Munshea A. Global prevalence and associated risk factors of pre eclampsia and eclampsia: A systematic review and meta analysis. PLoS One. 2020; 15(9): e0239048. DOI: https://doi.org/10.1371/journal.pone.0237600
Matsubara K, Higaki T, Matsubara Y, Nawa A. Nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia. Int J Mol Sci. 2015; 16(3): 4600-14. DOI: https://doi.org/10.3390/ijms16034600
Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre eclampsia: Pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019; 15(5): 275–89. DOI: https://doi.org/10.1038/s41581-019-0119-6
Burton GJ, Redman CW, Roberts JM, Moffett A. Pre eclampsia: pathophysiology and clinical implications. BMJ. 2019; 366: I2381. DOI: https://doi.org/10.1136/bmj.l2381
Huppertz B. Traditional and new routes of trophoblast invasion and their implications for pregnancy diseases. Int J Mol Sci. 2020; 21(1): 289. DOI: https://doi.org/10.3390/ijms21010289
Lei J, Zhao M, Li L, Ji B, Xu T, Sun M, et al. Research progress of placental vascular pathophysiological changes in pregnancy induced hypertension and gestational diabetes mellitus. Front Physiol. 2022; 13: 954636. DOI: https://doi.org/10.3389/fphys.2022.954636
Susanto H, Aulanni’am A, Wuragil DK, Taufiq A, Sunaryono S, Trijoyo Purnomo JD. Betatrophin: A promising biomarker for metabolic syndrome and diabetes mellitus risk screening in teenagers. Indonesian J Med Lab Sci Tech. 2025; 7 (1): 1-11. DOI: http://dx.doi.org/10.33086/ijmlst.v7i1.6028
Xu F, Wang X, Ni Y, Wang J. Association of betatrophin with metabolic syndrome: A systematic review and meta analysis. Pathol Oncol Res. 2021; 27: 1609914. DOI: https://doi.org/10.3389/pore.2021.1609914
Kirlangic MM, Sahin ME, Sahin E, Madendag Y, Madendag IC, Akdemir E, et al. First trimester maternal serum betatrophin levels are decreased in pregnancies complicated by gestational diabetes mellitus. Placenta. 2022; 124: 1–4. DOI: https://doi.org/10.1016/j.placenta.2022.05.001
Bughio R, Memon S, Rajper F, Goswami P, Parveen K. Placental histo-morphometric changes in preeclampsia and its association with betatrophin. J Population Therap Clin Pharmacol. 2024; 31(6): 437-444. DOI: https://doi.org/10.53555/jptcp.v31i6.6336
Akdemir E, Sahin E, Madendag Y, Sahin ME, Madendag IC, Acmaz G, et al. Effect of preeclampsia and preeclampsia severity on insulin, HOMA-IR, and betatrophin levels in non-diabetic pregnant women. Placenta. 2019; 84(1): 33–38. DOI:https://doi.org/10.1016/j.placenta.2020.07.018
Akdemir E, Sahin E, Madendag Y, Sahin ME, Madendag IC, Acmaz G, Ozdemir F, Muhtaroglu S, Muderris II. Effect of preeclampsia and preeclampsia severity on insulin, HOMA-IR, and betatrophin levels in non-diabetic pregnant women. Placenta. 2020; 100: 54-9. DOI:https://doi.org/10.1016/j.placenta.2020.07.018
Onalan E, Bozkurt A, Gursu MF, Yakar B, Donder E. Role of betatrophin and inflammation markers in type 2 diabetes mellitus, prediabetes and metabolic syndrome. J Coll Physicians Surg Pak 2022; 32(03): 303-7. DOI: https://doi.org/10.29271/jcpsp.2022.03.303
Erol O, Ellidağ HY, Ayık H, Özel MK, Derbent AU, Yılmaz N. Evaluation of serum betatrophin levels in pregnant women with gestational diabetes mellitus. Gynecol Endocrinol. 2015; 31(8): 652-6. DOI: https://doi.org/10.3109/09513590.2015.1056 142
Le QA, Akhter R, Coulton KM, Vo NTN, Duong LTY, Nong HV, et al. Periodontitis and preeclampsia in pregnancy: a systematic review and meta analysis. Matern Child Health J. 2021. DOI: https://doi.org/10.1007/s10995-022-03556-6
Akasaki Y. Angiogenic factors for early prediction of preeclampsia. Hypertens Res. 2024; 47 (10): 2959-60. DOI: https://doi.org/10.1038/s41440-024-01846-w
Bisson C, Rajan RS, Rana S. Angiogenic Biomarkers for Preeclampsia in Clinical Setting: A New Era. Hypertension. 2025; 232(4): 385.e1–385.e21. DOI: https://doi.org/10.1161/HYPERTENSIONAH A.123.21686
Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. ISSHP classification, diagnosis & management of hypertensive disorders of pregnancy. Hypertension. 2018; 13: 291–310. Available from: https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.117.10803
Staff AC, Benton SJ, von Dadelszen P, Roberts JM, Taylor RN, Powers RW, et al. Redefining preeclampsia using placenta derived biomarkers. Hypertension. 2013; 61(5): 932–42. DOI: https://doi.org/10.1161/hypertensionaha.111.00250
Rana S, Karumanchi SA, Lindheimer MD. Angiogenic factors in diagnosis and management of preeclampsia. Hypertension. 2014; 63(2): 198–202. DOI: https://doi.org/10.1161/hypertensionaha .113.02293
Dimitriadis E, Rolnik DL, Zhou W, Estrada-Gutierrez G, Koga K, Francisco RPV, et al. Pre-eclampsia. Nat Rev Dis Primers. 2023; 9(1): 8. DOI: https://doi.org/10.1038/s41572-023-00417-6
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Editor Office

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Readers may “Share-copy and redistribute the material in any medium or format” and “Adapt-remix, transform, and build upon the material”. The readers must give appropriate credit to the source of the material and indicate if changes were made to the material. Readers may not use the material for commercial purpose. The readers may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
