Pathogenetic significance of vascular endothelial growth factor and prostaglandin F2α in the development of pregnancy loss in cytomegalovirus infection
https://doi.org/10.36604/1998-5029-2025-95-109-115
Abstract
Introduction. In the past decade, vascular growth factors and prostaglandins have been actively studied in the context of angiogenesis regulation and their role in pregnancy pathologies. A review of the current literature reveals a lack of data proving the involvement of vascular endothelial growth factor (VEGF) A and prostaglandin (PG) F2α in the pathogenesis of early pregnancy loss associated with exacerbation of cytomegalovirus (CMV) infection.
Aim. To investigate the levels of VEGF-A and PG F2α in peripheral blood and determine their prognostic significance in pregnancy loss during exacerbation of chronic CMV infection at 6–7 weeks of gestation.
Materials and methods. A case-control study was conducted, involving 65 pregnant women. The main group included 35 patients experiencing exacerbation of chronic CMV infection at 6–7 weeks of pregnancy. The control group consisted of 30 practically healthy women at 6–7 weeks of pregnancy. CMV infection was diagnosed by the presence of IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA) and the detection of CMV DNA by polymerase chain reaction (PCR). Serum VEGF-A and PG F2α levels were measured using ELISA.
Results. During exacerbation of CMV infection at 6–7 weeks of pregnancy, a decrease in VEGF-A concentration to 10.35 ± 0.05 ng/mL was observed, along with an increase in PG F2α levels to 1092 ± 13.33 pg/mL, compared to the control group values (16.56 ± 0.04 ng/mL and 720 ± 9.21 pg/mL, respectively). To analyze the selected evaluation criteria, a discriminant function with a probability of differences of at least 95% was determined. A discriminant equation was derived for this study, which has the form: PI = -231.377 + 13.694 × VEGF-A + 0.052 × PG F2α, where PI is the discriminant function with a threshold value of -32.92. When PI is equal to or greater than the threshold value, it is possible to predict the risk of pregnancy loss at 6–7 weeks of gestation during an exacerbation of cytomegalovirus infection. A PI less than the threshold value indicates the absence of such a risk during this period of pregnancy.
Conclusion. The obtained results confirm the pathogenetic significance of VEGF-A and PG F2α dysregulation in the development of pregnancy loss during CMV infection exacerbation at 6–7 weeks. These findings may serve as the basis for expanding diagnostic and therapeutic approaches in this pathology.
About the Authors
N. A. IshutinaRussian Federation
Nataliа A. Ishutina, PhD, D.Sc. (Biol.), Professor of FEB RAS, Leading Staff Scientist of Laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases
22 Kalinina Str., Blagoveshchensk, 675000
I. A. Andrievskaya
Russian Federation
Irina A. Andrievskaya, PhD, D.Sc. (Biol.), Professor of RAS, Head of Laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases
22 Kalinina Str., Blagoveshchensk, 675000
I. V. Dovzhikova
Russian Federation
Inna V. Dovzhikova, PhD, DSc (Biol.), Leading Staff Scientist, Laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases
22 Kalinina Str., Blagoveshchensk, 675000
N. N. Dorofienko
Russian Federation
Nikolay N. Dorofienko, PhD (Med.), Senior Staff Scientist, Laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases
22 Kalinina Str., Blagoveshchensk, 675000
References
1. Bylym G.V., Noskova O.V., Litvinova YE.V., Korobova M.I., Churilov A.A. [Purpose of the work: to study the principles of pregravid training in women with recurrent miscarriage]. Vestnik gigiyeny i epidemiologii = Vestnik of hygiene and epidemiology 2022; 26(3):237–241 (in Russian).
2. Sushko T.A., Yeremeyeva D.R., Zaynulina M.S. [Role of herpesvirus infections in the genesis of reproductive losses]. Akusherstvo i ginekologiya Sankt-Peterburga = Obstetrics and gynaecology of St. Petersburg 2019; 2:44–48 (in Russian).
3. Dzhumagaliyeva A.S., Aktaeva L.M., Icenova C.Sh., Egle B., Sanatbayeva A.A., Yuan' D.L., Abisheva A.O. [Modern data of the role of infectious and inflammatory processes in the etiology of preterm birth]. Vestnik Kazahskogo nacional'nogo medicinskogo universiteta = Vestnik KazNMU. 2018; 4:1–6 (in Russian).
4. Osmonaliyeva S.T. [Spontaneous abortion: clinicomorphological aspects]. Vestnik Kyrgyzskoy gosudarstvennoy meditsinskoy akademii imeni I.K. Akhunbayeva = Vestnik of KSMA named after I.K. Akhunbaev 2013; 2:104–108 (in Russian).
5. Bragina T.V., Petrov Yu.A., Arndt I.G., Yevdokimova YE.P., Chernavskiy V.V. [Clinical-diagnostic and pathogenetic aspects of non-developing pregnancy]. Mediko-farmatsevticheskiy zhurnal «Pul's» = Medical & pharmaceutical journal «Pulse» 2020; 22(10):6–9 (in Russian). https://doi.org/10.26787/nydha-2686-6838-2020-22-10-6-9
6. Demchenko N.S., Bashmakova N.V., Tret'yakova T.B. [Pathogenesis of the pregnancy loss: role of the vascular endothelial growth factor (VEGF-A)]. Ural'skiy meditsinskiy zhurnal = Ural Medical Journal 2012; 11(103):26–29 (in Russian).
7. Burton G.J., Charnock-Jones D.S., Jauniaux E. Regulation of vascular growth and function in the human placenta. Reproduction 2009; 138(6):895-902. https://doi.org/10.1530/REP-09-0092
8. Gonsalez-Pacheco F.R., Deudero J.J., Castellanos M.C., Castilla M.A., Alvarez-Arroyo M.V., Yagüe S., Caramelo C. Mechanisms of endothelial response to oxidative aggression: protective role of autologous VEGF and induction of VEGFR2 by H2O2. Am. J. Physiol. Heart. Circ. Physiol. 2006; 291(3):1395–1401. https://doi.org/10.1152/ajpheart
9. Ul'yanina Ye.V., Fatkullin I.F. [Vascular endothelial growth factor role in predicting vascular disorders in pregnant with fetal growth restriction syndrome]. Kazanskiy meditsinskiy zhurnal = Kazan Medical Journal 2015; 96(2):220–223 (in Russian). https://doi.org/10.17750/KMJ2015-220
10. En'kova Ye.V., Khoperskaya O.V. [The value of determining concentrations of calcidiol and vascular endothelial growth factor to predict non-developing pregnancy]. Nauchn·yye rezul'taty biomeditsinskikh issledovaniy = Research results in biomedicine 2018; 4(4):69–78 (in Russian). https://doi.org/10.18413/2313-8955-2018-4-4-0-8
11. Kim M., Park H.J., Seol J.W., Jang J.Y., Cho Y.S., Kim K.R., Choi Y., Lydon J.P., Demayo F.J., Shibuya M., Ferrara N., Sung H.K., Nagy A., Alitalo K., Koh G.Y. VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodeling during pregnancy. EMBO Mol. Med. 2013; 5(9):1415–1430. https://doi.org/10.1002/emmm.201302618
12. Ishutina N.A., Andrievskaya I.A., Dovzhikova I.V., Dorofienko N.N., Gorikov N.N. [Effect of oxidative stress and fatty acids disbalance on the development of apoptosis in the placenta with cytomegalovirus infection in the first trimester] Acta Biomedica Scientifica 2019; 4(2):16–22 (in Russian). https://doi.org/10.29413/ABS.2019-4.2.2
13. Gomez-Lopez N., Romero R., Plazyo O., Panaitescu B., Furcron A.E., Miller D., Roumayah T., Flom E., Hassan S.S. Intra-amniotic administration of HMGB1 induces spontaneous preterm labor and birth. Am. J. Reprod. Immunol. 2016; 75(1):3–7. https://doi.org/10.1111/aji.12443
14. Nikolayeva A.S., Tanysheva G.A. [Modern aspects of prediction and prevention of preterm labor according to published data. literature review]. Nauka i zdravookhraneniye = Science & Healthcare 2019; 21(5):23–36 (in Russian).
15. Pozzi A, Zent R. Regulation of endothelial cell functions by basement membrane- and arachidonic acid-derived products. Wiley Interdiscip. Rev. Syst. Biol. Med. 2009; 1(2):254–272. https://doi.org/10.1002/wsbm.7
16. Kaczynski P., Goryszewska E., Baryla M., Waclawik A. Prostaglandin F2α stimulates angiogenesis at the embryomaternal interface during early pregnancy in the pig. Theriogenology 2020; 15(142):169–176. https://doi.org/10.1016/j.theriogenology.2019.09.046
17. Wang Y., Wang J.N., Liu Z.J., Wei X., Xiao X., Wang D.W. [Arachidonic acid epoxygenases and their metabolites promote angiogenesis]. Zhonghua Xin Xue Guan Bing Za Zhi 2005; 33(12):1122–1131 (in Chinese).
18. Banerjee P., Ghosh S., Dutta M., Subramani E., Khalpada J., Roychoudhury S., Chakravarty B., Chaudhury K. Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage. PLoS One 2013; 8(11):e80940. https://doi.org/10.1371/journal.pone.0080940
19. Tabolova V.K., Korneyeva I.E., Donnikov A.E., Burmenskaya O.V., Maslova M.A., Smol'nikova V.Yu. [The local endometrial expression profile of the growth factor and cytokine genes during the implantation window in chronic endometritis]. Akusherstvo i ginekologiya = Obstetrics and Gynecology 2014; 12:74–78 (in Russian).
Review
For citations:
Ishutina N.A., Andrievskaya I.A., Dovzhikova I.V., Dorofienko N.N. Pathogenetic significance of vascular endothelial growth factor and prostaglandin F2α in the development of pregnancy loss in cytomegalovirus infection. Bulletin Physiology and Pathology of Respiration. 2025;(95):109-115. (In Russ.) https://doi.org/10.36604/1998-5029-2025-95-109-115