Abstract
A comparative morphological study was carried out to analyze the number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 categorized by the disease severity. The number of syncytial knots was assessed on specimens stained with hematoxylin and eosin. VEGF expression was determined by immunohistochemical analysis in syncytiotrophoblast and villous endothelial cells. Morphological study of the placenta tissue of parturient women with COVID-19 showed increased numbers of syncytial knots in the villi, indicating the development of preplacental hypoxia. High VEGF expression in syncytiotrophoblast and vascular endotheliocytes reflects a stereotyped response to hypoxia and can underlie the development of a preeclampsia-like syndrome. The number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 depended on the disease severity.
Key Words: novel coronavirus infection (COVID-19), SARS-CoV-2, placenta, syncytial knots, VEGF
Footnotes
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 171, No. 3, pp. 386-390, March, 2021
References
- 1.Shchegolev AI, Lyapin VM, Tumanova UN, Vodneva DN, Shmakov RG. Histological changes in the placenta and vascularization of its villi in early- and late-onset preeclampsia. Arkh. Patol. 2016;78(1):13–18. doi: 10.17116/patol201678113-18.Russian. [DOI] [PubMed] [Google Scholar]
- 2.Shchegolev AI, Tumanova UN, Lyapin VN, Serov VN. The syncytiotrophoblast of the placental villi in health and in preeclampsia. Akush. Ginekol. 2020;(6):21-28. doi: 10.18565/aig.2020.6.21-28. Russian.
- 3.Shchegolev AI, Tumanova UN, Serov VN. Placental lesions in pregnant women with SARS-CoV-2 infection. Akush. Ginekol. 2020;12:44–52. doi: 10.18565/aig.2020.12.44-52. [DOI] [Google Scholar]
- 4.Bergmann A, Ahmad S, Cudmore M, Gruber AD, Wittschen P, Lindenmaier W, Christofori G, Gross V, Gonzalves A, Ch, Gröne HJ, Ahmed A, Weich HA. Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model. J. Cell. Mol. Med. 2010;14(6B):1857-1867.doi: 10.1111/j.1582-4934.2009.00820.x [DOI] [PMC free article] [PubMed]
- 5.Coronavirus disease 2019 (COVID-19). Situation Report — 51. WHO, 11 March 2020. URL: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10
- 6.Di Mascio D, Khalil A, Saccone G, Rizzo G, Buca D, Liberati M, Vecchiet J, Nappi L, Scambia G, Berghella V, D’Antonio F. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and metaanalysis. Am. J. Obstet. Gynecol. MFM. 2020;2(2):100107. doi: 10.1016/j.ajogmf.2020.100107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Heazell AE, Moll SJ, Jones CJ, Baker PN, Crocker IP. Formation of syncytial knots is increased by hyperoxia, hypoxia and reactive oxygen species. Placenta. 2007;28(Suppl A):S33-S40. doi: 10.1016/j.placenta.2006.10.007 [DOI] [PubMed]
- 8.Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271–280.e8. doi: 10.1016/j.cell.2020.02.052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Hunter A, Aitkenhead M, Caldwell C, McCracken G, Wilson D, McClure N. Serum levels of vascular endothelial growth factor in preeclamptic and normotensive pregnancy. Hypertension. 2000;36(6):965–969. doi: 10.1161/01.hyp.36.6.965. [DOI] [PubMed] [Google Scholar]
- 10.Juan J, Gil MM, Rong Z, Zhang Y, Yang H, Poon LC. Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review. Ultrasound Obstet. Gynecol. 2020;56(1):15–27. doi: 10.1002/uog.22088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Khalid ME, Ali ME, Ali KZ. Full-term birth weight and placental morphology at high and low altitude. Int. J. Gynaecol. Obstet. 1997;57(3):259–265. doi: 10.1016/s0020-7292(97)00067-2. [DOI] [PubMed] [Google Scholar]
- 12.Mendoza M, Garcia-Ruiz I, Maiz N, Rodo C, Garcia-Manau P, Serrano B, Lopez-Martinez RM, Balcells J, Fernandez-Hidalgo N, Carreras E, Suy A. Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study. BJOG. 2020;127(11):1374–1380. doi: 10.1111/1471-0528.16339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J. Mol. Histol. 2020;51(6):613–628. doi: 10.1007/s10735-020-09915-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Redline RW, Boyd T, Campbell V, Hyde S, Kaplan C, Khong TY, Prashner HR, Waters BL; Society for Pediatric Pathology, Perinatal Section, Maternal Vascular Perfusion Nosology Committee. Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns. Pediatr. Dev. Pathol. 2004;7(3):237-249. doi: 10.1007/s10024-003-8083-2 [DOI] [PubMed]
- 15.Su M, Hu Z, Dong C, Xu X. Vascular endothelial growth factor gene polymorphisms and hypertensive disorder of pregnancy: A meta-analysis. Pregnancy Hypertens. 2019;17:191–196. doi: 10.1016/j.preghy.2019.05.012. [DOI] [PubMed] [Google Scholar]