Effect of Oxidative Stress and Fatty Acids Disbalance on the Development of Apoptosis in the Placenta with Cytomegalovirus Infection in the First Trimester

Background. Reactivation of cytomegalovirus infection (CMV) during pregnancy is associated with manifestation of oxidative stress, both in the maternal peripheral blood and in the placental tissues. One of the effects of oxidative stress is a disturbance of the metabolism of fatty acids, which leads to the initiation of the apoptotic cascade, the death of trophoblast cells and, as a result, tissue or organ dysfunction, promoting to the development of a pathological condition. However, an analysis of the current literature indicates insufficient information on this problem in the villous chorion of the placenta in CMV infection.

Aims. To study the relationship between the oxidative stress development and fatty acid imbalance in apoptosis of trophoblast cells during reactivation of CMV in the first trimester.

Material and methods. We examined peripheral blood, urine, a homogenate of the villous chorions from 35 pregnant women with CMV reactivation within 9–11 weeks of pregnancy and from 30 pregnant women without CMV of the same gestation period. We studied levels of IgM and IgG for cytomegalovirus, low-avid IgG antibodies to cytomegalovirus (avidity index), phospholipase A2 content, fatty acid content, number of apoptotic trophoblast cells, fatty acid peroxide content and catalase activity. Sampling and analysis of material from pregnant women was conducted in 2016–2018.

Results. The reactivation of CMV in the first trimester of pregnancy led to an increase content in the phospholipase A2 in villous chorion by 2.5 times, by 1.5 times of fatty acid peroxides, 1.5 times arachidonic acid, palmitic acid by 1.3 times, number of trophoblast cells in a state of apoptosis by 4.7 times and decrease catalase activity by 1.44 times.

Conclusion. As a result of the study, cytomegalovirus-dependent induction of oxidative stress and imbalance of fatty acids triggering apoptosis of trophoblast cells was identified. Increased apoptosis initiates inflammation and destructive processes in the early placenta.

1. Duhig K, Chapell LC, Shennan AH. Oxidative stress in pregnancy and reproduction. Obstet Med, 2016; 9(3): 113-116. doi: 10.1177/1753495X16648495

2. Uspenskaya YuB, Sheptulin AA, Kuznetsova IV, Goncharenko NV, Gerasimov AN. Role of antioxidant defense disorders during intrahepatic cholestasis of pregnant women and development of gestational complications. Meditsinskiy alfavit. 2018; 2(13): 26-30. (In Russ.)

3. Ishutina NA, Dorofienko NN. Lipid peroxidation in pregnancy complicated by cytomegalovirus infection. Bulleten fisiologii i patologii dykhaniya. 2014; 54: 66-69. (In Russian)

4. Murata M, Fukushima K, Takao N, Seki H, Takeda S, Wake N. Oxidative stress producent by xanthine oxidase induces apoptosis in human extrtravillous trophoblast cells. J Reprod Der. 2013; 59(1): 7-13. doi: 10.1262/jrd.2012-053

5. Khovkhaeva PA, Krasnyy AM, Tyutyunik NV, Sergunina OA, Ganichkina MB, Amiraslov EYu, et al. Apoptosis in the placenta with preeclampsia. Meditsinskiy sovet. 2016; 2: 102-103 (In Russ.)

6. Listenberg LL., Han X, Lewis SE, Cases S. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. PNAS. 2003; 100: 3077-3082. doi: 10.1073/pnas.0630588100

7. Wietrak E, Kamiński K, Leszczyńska-Gorzelak B, Oleszczuk J. Effect of Docosahexaenoic acid on apoptosis and proliferation in the placenta: preliminary report. Biomed Res Int. 2015; 2015: 482875. doi:10.1155/2015/482875

8. Lutsenko MT, Andrievkaya IA. The degree of apoptosis in syncytiotrophoblast nuclei placental villi with herpes viral infections. Morfologiya. 2009: 135(1): 45-48. (In Russ.)

9. Ishutina NA, Lutsenko MT, Dorofienko NN. The role of palmitic acid in implementation of apoptosis in cytomegalovirus infection in the gestation period. Sibirskiy meditsinskiy zhurnal (Irkutsk). 2014; 1: 11-14 (In Russ.)

10. Lilli P. Pathohistological technique and practical histochemistry. M.: Mir; 1969 (In Russ.)

11. Gayer G. Electronic histochemistry. M.: Mir; 1973. (In Russ.)

12. Carren JP, Dubacq JPJ. Adaptation of a macro-scale method to the micro-scale for fatty acid methyl transesterification of biological lipid extracts. Chromatography. 1978; 151: 384-390.

13. Prokopenko VM. Role of oxidative stress in the pathogenesis of preeclampsia. Zhurnal akusherstva i zhenskikh bolezney. 2004; 4: 31-36 (In Russ.)

14. Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, et al. Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int Hindawi. 2014; 2014: 761264. doi: 10.1155/2014/761264

15. Ota T, Gayet C, Ginsberg HN. Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. J Clin Invest. 2008; 118(1): 316-332. doi: 10.1172/JCI32752

16. Guo W, Wong S, Xie W, Lei T, Luo Z. Palmitate modulates intracellular signaling, induced endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L-1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab. 2007; 293(2): E576-586. doi: 10.1152/ajpendo.00523.2006

17. Zhang Y, Yang X, Shi H, Dong L, Bai J. Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes. Lipids Health Dis. 2011; 10: 122-127. doi: 10.1186/1476-511X-10-122