Immunohistochemical evaluation of extravillous cytotrophoblasts in the uteroplacental bed in iron-deficiency anemia of pregnancy

Abstract

Background: Iron deficiency anemia (IDA) in pregnancy is challenging, inducing a systemic pathological process in women's bodies. In this context, impaired protein metabolism, decreased respiratory enzyme activity, limitation of cells' proliferative potential, oxidative stress, hypoxia, and endothelial dysfunction affect the “mother-placenta-fetal” system. However, several features of this pathogenetic cascade, including the spread of extravillous cytotrophoblasts (ECT), are yet to be investigated. This research aimed to study the immunohistochemical features and quantitative indicators of ECT spread throughout the uteroplacental bed (UPB) in IDA at 37–40-week gestation. Methods: Eighty biopsies of UPB and myometrium were studied postcesarean section with the previous observation of physiological pregnancy and gestation in IDA conditions without clinical signs of placental insufficiency. Histological sections were performed on immunohistochemical techniques with primary antibodies against metalloproteinases 2 and 9, placental lactogen, and antiapoptotic protein BCL-2. Their quantitative parameters in the cytoplasm of endovascular CT cells were determined using computer microdensitometry by calculating optical color density. The arithmetic mean and its statistical error were calculated. The Shapiro–Wilk test of normality was performed. The comparisons between the groups were provided on the unpaired two-tailed Student's test. Results: The analysis of the depth of CT invasion on the material of the UPB and the myometrium in conditions of IDA showed the spread of the CT invasion not only in the area of the spiral arteries of the endometrium but also the incorporation of endovascular CT into the myometrial arteries walls. Immunohistochemical study of CT invasion showed the following results: during physiological pregnancy, the concentration of metalloproteinase 2 was 0.232 ± 0.0012 optical density units (ODU), metalloproteinase 9 - 0.219 ± 0.0014 ODU. Immunovisualization of placental lactogen during physiological pregnancy was 0.314 ± 0.0022 ODU in interstitial CT and 0.109 ± 0.0022 ODU in endovascular CT; in the conditions of IDA: 0.337 ± 0.0022 ODU in interstitial CT and 0.110 ± 0.0022 ODU in endovascular CT. Conclusion: It is established that, during gestation with IDA, a deepening of CT invasion in the structure of the UPB, an increase in the lining distance of the endothelium-replacing CT in the artery walls, and consequently, a dilatation of spiral and radial arteries takes place in the uterus of pregnant women. However, the invasive ability and synthetic activity of the CT and as a result, the adequacy of the gestational transformation of UPB structures are affected by the hypoxia and depend on the degree of IDA of pregnant women.

Keywords

• uteroplacental bed
• cytotrophoblast invasion
• extravillous cytotrophoblasts
• metalloproteinases
• iron-deficiency anemia in pregnancy
• gynecology