Comparative analysis of plasma betatrophin levels with placental dysfunction in preeclamptic pregnancies: A histopathological and biochemical study

Authors

  • Rabia Bughio Liaquat University of Medical and Health Sciences; Jamshoro Pakistan
  • Khalida Parveen Liaquat University of Medical and Health Sciences; Jamshoro Pakistan
  • Amber Abdul Ghani Liaquat University of Medical and Health Sciences; Jamshoro Pakistan
  • Anas Raza Liaquat University of Medical and Health Sciences; Jamshoro Pakistan
  • Sana Shabbir Liaquat University of Medical and Health Sciences; Jamshoro Pakistan
  • Reema Laghari Liaquat University of Medical and Health Sciences; Jamshoro Pakistan

DOI:

https://doi.org/10.55629/pakjpathol.v36i2.903

Abstract

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

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Published

30-06-2025

How to Cite

1.
Bughio R, Parveen K, Ghani AA, Raza A, Shabbir S, Laghari R. Comparative analysis of plasma betatrophin levels with placental dysfunction in preeclamptic pregnancies: A histopathological and biochemical study . Pak J Pathol [Internet]. 2025 Jun. 30 [cited 2026 Oct. 28];36(2):130-7. Available from: https://pakjpath.com/index.php/Pak-J-Pathol/article/view/903