Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.
Department of Clinical and Experimental Medicine, Section of Legal Medicine, University of Foggia, Viale Europa 12, 71122 Foggia, Italy.
Int J Mol Sci. 2023 Jul 30;24(15):12221. doi: 10.3390/ijms241512221.
During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36-42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.
在妊娠期间，活性氧（ROS）作为胎盘中血流生理学的关键信号分子。氧化应激被认为是维持缺氧缺血性脑病（HIE）发病和进展的原因。对 36-42 周妊娠的胎儿和新生儿的大脑和胎盘进行了回顾性研究（组 1：胎儿宫内死亡，组 2：分娩中死亡，组 3：产后死亡，对照组新生儿猝死）；所有组进一步分为两个亚组（脑亚组 B [brain] 和胎盘亚组 P [placenta]），并通过氧化应激标志物（NOX2、8-OHdG、NT、iNOS）、IL-6 的免疫组织化学研究进行研究，并且仅在脑样本上，AQP4。脑样本的结果表明，NOX2、8-OHdG、NT、iNOS 和 IL-6 的表达明显高于对照组。iNOS 在胎儿宫内死亡（组 1）中表达更多，而在产后死亡（组 3）中表达较少，而在分娩中死亡（组 2）中，免疫反应性非常低。IL-6 在胎儿宫内死亡（组 1）的大脑皮质中表达最高，而分娩中死亡（组 2）和产后死亡（组 3）的免疫反应性较弱。产后死亡（组 3）胎盘对 NOX2 的免疫反应性最高，几乎是胎儿宫内死亡（组 1）和分娩中死亡（组 2）胎盘的两倍。胎儿宫内死亡（组 1）和分娩中死亡（组 2）胎盘组织中 iNOS 的表达高于产后死亡（组 3），而胎儿宫内死亡（组 1）的 IL-6 表达高于产后死亡（组 3）。AQP4 被排除为可能的标志物，因为三组病例和对照组的免疫组织化学反应均为阴性。从法医病理学的角度来看，本研究的目的是为产科领域的医疗责任案例提供科学证据，以支持 HIE 时间的临床数据。
