Contents lists available at ScienceDirect Pregnancy Hypertension journal homepage: www.elsevier.com/locate/preghy Elevated immunoexpression of interferon-gamma in placenta tissue samples from pregnancies complicated with preeclampsia compared to the placenta previa Nadia Sheibak a,b , Hamidreza Mahmoudzadeh-Sagheb a,b , Bita Moudi a,b , Zahra Heidari a,b, ⁎ a Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran b Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran ARTICLE INFO Keywords: Placenta previa Preeclampsia Pregnancy complications Interferon-gamma Trophoblast ABSTRACT Aim: The present study aimed to compare the immunohistochemical expression of interferon-gamma (IFN-γ) in placentas from pregnancies complicated with preeclampsia (PE) and placenta previa (PP) and normal healthy placentas. Methods: Placentas were collected from cases of PE, PP and normal pregnancies as a control group (10 placentas in each group). All the deliveries were at full-term (37–42 weeks) by cesarean section and newborns were without any complications or diseases. Expression of IFN-γ in the placenta was determined using im- munohistochemical methods and fndings were compared. Statistical analysis was performed by Mann-Whitney and Kruskal-Wallis tests for comparing the mean values of IFN-γ expression in the placentas from PE, PP and control groups. Our results showed that the immunoexpression of IFN-γ in syncytiotrophoblast cells, extravillous trophoblast cells, vascular endothelium and basal plate of the placenta from PE group were more than control and PP groups (P < 0.05) and in PP group were more than the control group (P < 0.05). Conclusion: We concluded that the immunoexpression of IFN-γ was increased signifcantly in placenta tissue samples of the PE group compared to the PP group and normal pregnancies. It is proposed that IFN-γ has an important role in the diferent mechanisms of PE and PP progression. 1. Introduction The principal part of the placenta, which has direct interaction with the mother’s uterus and also has a principal role in the outcomes of pregnancy, is the trophoblast [1,2]. Implantation of the embryo in the decidua of the uterus is mediated by a deep invasion of extravillous trophoblast cells (EVTs) which arise from this cell population [2–5]. Remodeling of uterine spiral arteries is another important event in the development of the placenta during normal pregnancy. Both of these essential processes need precise control and regulating [3,6]. It has been reported that changes of the invasiveness of EVTs and count of this cell population in the placental bed due to the apoptosis or proliferation processes might be the major mechanism that regulates the invasion of these cells [6]. As it was investigated in our previous studies on quantitative changes of EVTs in placenta tissues from mo- thers with some pregnancy complications [7,8]. The role of trophoblast in pregnancy complications was investigated previously [1,9–11]. There are several published reports on the association of EVTs’ invasion throughout the decidua with the immune system and infammatory responses. In addition, it has been shown that mediators of infammation usually release during normal placentation [4]. Interferon-gamma (IFN-γ), a regulatory cytokine of the immune response [12,13], is one of these factors that have a substantial function in the maintenance of gestation. It is primitively produced in the healthy placenta [14–16]. It has been suggested that IFN-γ probably involves in the development and surviving the placental cytotropho- blast by controlling the apoptosis rate of these cells [15,17]. It has been shown that high levels of IFN-γ were associated with a harmful condition for the fetus and defected development and function of the placenta and led to the progression of pregnancy complications. Probably, immune-related disorders in the angiogenesis during pla- centation that is mediated by IFN-γ could be a potential agent that is involved in the fetus vulnerability and complicated pregnancy [2,4,15]. On the other hand, elevated count of dNKs at the implantation site probably control and progress the invasion of EVTs by cytokine https://doi.org/10.1016/j.preghy.2020.08.003 Received 25 January 2020; Received in revised form 9 August 2020; Accepted 27 August 2020 ⁎ Corresponding author at: Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. E-mail address: histology_iri@yahoo.com (Z. Heidari). Pregnancy Hypertension 22 (2020) 175–180 Available online 11 September 2020 2210-7789/ © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved. T