Immunohistochemical assessment of epidermal growth factor receptor and prohibitin expression in “post-COVID” placentas: results of a comparative cross-sectional study

Authors

DOI:

https://doi.org/10.18370/2309-4117.2024.72.77-86

Keywords:

pregnancy, COVID-19, immunohistochemical study of the placenta, epidermal growth factor, prohibitin

Abstract

Background. COVID-19 pandemic is accompanied by a considerable number of morbidity cases among pregnant women. Certain knowledge has been accumulated about the histopathological features of the placenta during SARS-CoV-2 infection. Specific proteomic studies of the function of the placenta are insufficient.
Objective of the study: to study the perinatal outcomes of pregnancy and histopathological features of the placenta and the expression of epidermal growth factor receptors (EFGR) and prohibitin (PHB) in the placenta in pregnant women with COVID-19 infection in comparison with data in a group of healthy pregnant women without a COVID-19 history.
Materials and methods. 58 pregnant women with COVID-19 infection during pregnancy and 40 healthy pregnant women were examined at the base of Maternity Hospital No. 2 of the Odessa City Council. A histological and immunohistochemical study of placentas was carried out for the expression of EFGR and PHB In addition to a general clinical examination.
Results. A higher frequency of premature births (15.51% vs 5%) and cesarean sections (34.4% vs 12.5%) in the “post-COVID” group was revealed. Most women fell ill in the third trimester of pregnancy (65.51%). A significant difference was found in Apgar scores in the groups (6.48 ± 2.39 vs 8.05 ± 0.54 points), in the weight of newborns (3067.93 ± 620.21 g vs
3617.25 ± 354.58 g). In the placentas of the “post-COVID” group, signs of mother’s (53.45% vs 12.5%) and fetus’ vascular malperfusion (32.7% vs 15%) were detected with greater frequency; as well as hemodynamic disturbances (53.45% vs 15%). Analysis of EFGR expression in the groups showed no differences (2.96 ± 0.2 vs 2.75 ± 0.44) in contrast to PHB (1.52 ± 1.12 vs 0.25 ± 0.5), which was characterized by overexpression in the women with COVID-19.
Conclusions. SARS-CoV-2 infection during pregnancy is associated with certain changes in placental metabolism, and changes in the expression of placental proteins EGFR and PHB may be involved in the pathogenetic mechanisms of the placental dysfunction development. The limited sample size requires additional research.

Author Biographies

G.S. Manasova, Odessa National Medical University, Odessa

MD, professor, Department of Obstetrics and Gynecology

Y.O. Stasii, Odessa National Medical University; Communal non-commercial enterprise “Maternity hospital No. 5” of the Odessa City Council, Odessa

postgraduate student, Department of Obstetrics and Gynecology;
obstetrician-gynecologist, Obstetric Department

References

  1. Abbasian MH, Mahmanzar M, Rahimian K, et al. Global landscape of SARS-CoV-2 mutations and conserved regions. J Transl Med. 2023 Feb 25;21(1):152. DOI: 10.1186/s12967-023-03996-w.
  2. Fisher JJ, McKeating DR, Cuffe JS, et al. Proteomic Analysis of Placental Mitochondria Following Trophoblast Differentiation. Front Physiol. 2019 Dec 20;10:1536. DOI: 10.3389/fphys.2019.01536.
  3. Levitan D, London V, McLaren RA, et al. Histologic and Immunohistochemical Evaluation of 65 Placentas From Women With Polymerase Chain Reaction-Proven Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. Arch Pathol Lab Med. 2021 Jun 1;145(6):648–656. DOI: 10.5858/arpa.2020-0793-SA.
  4. Bouachba A, Allias F, Nadaud B, et al. Placental lesions and SARS-Cov-2 infection: diffuse placenta damage associated to poor fetal outcome. Placenta. Sep 1 2021;112:97–104. DOI: 10.1016/j.placenta.2021.07.288.
  5. Gharesi-Fard B, Zolghadri J, Kamali-Sarvestani E. Alteration in the expression of proteins in unexplained recurrent pregnancy loss compared with in the normal placenta. J Reprod Dev. 2014;60(4):261–7. DOI: 10.1262/jrd.2013-096.
  6. Patki S,Patil R, Patki S. Immunohistochemistry (I.H.C.) and Histopathology of the Fetoplacental Barrier in the Placentas of the Mothers, Recovered from Covid-19 Infection and its Clinical Significance. Acta Scientific Women’s Health 2021;3(10):33–37. DOI:10.31080/ASWH.2021.03.0284
  7. Man OM, Azamor T, Cambou M.C. et al. Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study. Nat Commun. 2024 Jan 24;15(1):399. DOI: 10.1038/s41467-023-44549-5.
  8. Foo SS, CambouMC, Mok T, et al. The systemic inflammatory landscape of COVID-19 in pregnancy: extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2. Cell Rep. Med. 2021; Nov 16;2(11):100453. DOI: 10.1016/j.xcrm.2021.100453.
  9. Sisman J, Jaleel MA, Moreno W, et al. Intrauterine transmission of SARS-COV-2 infection in a preterm infant. Pediatr Infect Dis J. Sep 2020;39(9):e265-e267. DOI: 10.1097/INF.0000000000002815.
  10. Schwartz DA, Baldewijns M, Benachi A, et al. Chronic histiocytic intervillositis with trophoblast necrosis is a risk factor associated with placental infection from coronavirus disease 2019 (COVID-19) and intrauterine maternal-fetal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in live-born and stillborn infants. Arch Pathol Lab Med. May 1 2021;145(5):517–528. DOI: 10.5858/arpa.2020-0771-SA.
  11. Rakheja D, Treat K, Timmons CF, et al. SARS-CoV-2 Immunohistochemistry In Placenta. Int J Surg Pathol. 2022 Jun;30(4):393–396. DOI: 10.1177/10668969211067754.
  12. Clemente L, Boeldt DS, Grummer MA, et al. Adenoviral transduction of EGFR into pregnancy-adapted uterine artery endothelial cells remaps growth factor induction of endothelial dysfunction. Mol Cell Endocrinol. 2020 Jan 1;499:110590. DOI: 10.1016/j.mce.2019.110590.
  13. Renshall LJ, Beards F, Evangelinos A, et al. Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction. Pharmaceutics. 2021; 13(11):1778. DOI: 10.3390/pharmaceutics13111778.
  14. Gulbiniene V, Balciuniene G, Petroniene J, et al. The Significance of Epidermal Growth Factor in Noninvasively Obtained Amniotic Fluid Predicting Respiratory Outcomes of Preterm Neonates. Int J Mol Sci. 2022 Mar 10;23(6):2978. DOI: 10.3390/ijms23062978.
  15. Li J, Wang L, Ding J, et al. Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration. Front Immunol. 2022 Apr 27;13:826198. DOI: 10.3389/fimmu.2022.826198.
  16. Yoshinaka T, Kosako H, Yoshizumi T, et al. Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region. iScience. 2019 Sep 27;19:1065–1078. DOI: 10.1016/j.isci.2019.08.056.
  17. Huo R, Zimmerman K, Weiss RM, et al. Cardiac-specific Deletion of Prohibitin-1 Leads to Fetal Demise, Gross Mitochondrial Abnormalities and Heart Failure in Adolescent Mice. Circulation Research. 2020;127:A359. DOI: 10.1161/res.127.suppl_1.359.
  18. Qu Y, Konrad C, AndersonC, Qian L, et al. Prohibitin S-Nitrosylation Is Required for the Neuroprotective Effect of Nitric Oxide in Neuronal Cultures Journal of Neuroscience. 2020 15 April,40(16):3142-3151. DOI: 10.1523/JNEUROSCI.1804-19.2020.
  19. Liu F, Zhang Y, Guo Z, Ren AJ. The Role of Prohibitin-2 in Diseases. Front. Biosci. (Landmark Ed). 2023, 28(9), 211. DOI: 10.31083/j.fbl2809211
  20. Palakkott AR, Alneyadi A, Muhammad K, et al. The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling. Vaccines (Basel). 2023 Mar 30;11(4):768. DOI: 10.3390/vaccines11040768.
  21. Engler M, Albers D, Von Maltitz P, et al. ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection. Life Sci Alliance. 2023 Jul 4;6(9):e202201880. DOI: 10.26508/lsa.202201880.
  22. Dülger SU, Mutlu N, Ceylan I, et al. The relationship between lung fibrosis, the epidermal growth factor receptor, and disease outcomes in COVID-19 pneumonia: a postmortem evaluation. Clin Exp Med. 2023 Aug;23(4):1181–1188. DOI: 10.1007/s10238-022-00872-7.
  23. de Morais Batista F, Puga MAM, da Silva PV, et al. Serum biomarkers associated with SARS-CoV-2 severity. Sci Rep 2022 Sep 26;12(1):15999. DOI: 10.1038/s41598-022-20062-5.
  24. Watanabe M, Arii J, Takeshima K, et al. Prohibitin-1 Contributes to Cell-to-Cell Transmission of Herpes Simplex Virus 1 via the MAPK/ERK Signaling Pathway. J Virol. 2021 Jan 13;95(3):e01413-20. DOI: 10.1128/JVI.01413-20.
  25. Yoshimoto FK. The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. Protein J. 2020 Jun;39(3):198-216. DOI: 10.1007/s10930-020-09901-4.
  26. Oyang L, Li J, Jiang X, et al. The function of prohibitins in mitochondria and the clinical potentials. Cancer Cell Int. Nov 8;22(1):343. DOI: 10.1186/s12935-022-02765-x
  27. Khong TY, Mooney EE, Ariel I, et al. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med. 2016 Jul;140(7):698-713. DOI: 10.5858/arpa.2015-0225-CC..
  28. Informer Technologies Inc. [Internet]. LUCIA G version 4.7 by Laboratory Imaging. Available from: https://lucia-g.software. informer.com/4.7/.
  29. Social Science Statistics. [Internet]. Available from: https://www.socscistatistics.com/tests/.
  30. Popescu DE, Roșca I, Jura AMC, et al. Prompt Placental Histopathological and Immunohistochemical Assessment after SARS-CoV-2 Infection during Pregnancy—Our Perspective of a Small Group. International Journal of Molecular Sciences. 2024; 25(3):1836. DOI: 10.3390/ijms25031836.
  31. Takahashi T, Sumi T, Michimata H, et al. Fatal diffuse alveolar hemorrhage caused by acute COVID-19 infection in an unvaccinated patient, QJM. 2023 Jul 28;116(7):521-522 Pages 521–522, DOI: 10.1093/qjmed/hcad018.
  32. Escamilla-Illescas D, Casas-Aparicio GA.Urinary epidermal growth factor as a protector in COVID-19 patients with AKI J Am Soc Nephrol. 2021;32:68.

Downloads

Published

2024-06-30

How to Cite

Manasova, G., & Stasii, Y. (2024). Immunohistochemical assessment of epidermal growth factor receptor and prohibitin expression in “post-COVID” placentas: results of a comparative cross-sectional study. REPRODUCTIVE ENDOCRINOLOGY, (72), 77–86. https://doi.org/10.18370/2309-4117.2024.72.77-86

Issue

No. 72 (2024)

Section

Scientific Studies

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

    1. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.