SPECIFIC FEATURES OF TLR9 EXPRESSION IN PLACENTAL TISSUE IN PREECLAMPSIA AND FETAL GROWTH RESTRICTION

Aim. To evaluate the level of TLR9 expression in placental tissue in cases of preeclampsia and fetal growth restriction. Material and methods. Histological study through staining with hematoxylin and eosin and immunohistochemical study using Ventana (Roche, UK) immunostainer (with a closed protocol for detection) were performed with the use of primary polyclonal antibodies to TLR9 (1:300; GenTex) on serial paraffin sections of placenta samples collected from 40 women at 26-39 weeks of gestation participating in the study. Of them, 18 women were diagnosed with severe preeclampsia, 12 - with moderate preeclampsia, 10 women were included in the control group. In 8 cases of severe preeclampsia (PE), intrauterine fetal growth restriction (IUGR) was detected. Comparative assessment of the optical density of staining was carried out using the nonparametric Mann-Whitney test. Results. In severe PE, including the cases complicated by IUGR, a significant increase in cytoplasmic as well as granular staining of TLR9 in villous cytotrophoblast and syncytiotrophoblast (STB) and in extravillous trophoblast (EVT) was detected. Moreover, the number of TLR9granules and their size in STB and EVT was associated with the severity of PE. The diameter of stained granules in STB in severe PE complicated by IUGR was significantly greater (1.27+0.41 ßm), compared to severe PE without IUGR (1.16+0.33 ßm) (p=0.05), as well as compared to moderate PE (1.13+0.41 ßm) (p=0.001), and the control group (1.09+0.30 ßm) (p=0.001). In severe PE complicated by IUGR, the maximum diameter of granules for EVT was 1.49+0.41 ßm, which was significantly greater than in severe PE without IUGR, in moderate PE, and in the control group (p=0.001). Granular staining was specific for cytotrophoblast and STB, as well as for placental macrophages (Kashchenko-Hofbauer cells). Conclusion. Thus, in severe preeclampsia, including the cases complicated by fetal growth restriction, a significant increase in cytoplasmic as well as granular staining of TLR9 in the villous cytotrophoblast and STB and in EVT was detected. Considering that an increase in TLR9 expression was associated with theproinflammatory response, the possibility of interaction between DNA fragments, including fetal DNA and damage-associated molecular patterns (DAMP), may underlie in the genesis of PE and development of systemic inflammatory response.

TLR9, granular staining, preeclampsia, placenta, trophoblast, TLR9