Perković Pavo, Štifter-Vretenar Sanja, Perković Marina, Štefančić Marko, Holjević Ena, Dekanić Andrea, Štimac Tea
Department of Gynecology and Obstetrics, University Hospital Merkur, Zajčeva 19, 10000 Zagreb, Croatia.
Department of Pathology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 161, 8200 Aarhus, Denmark.
Biomedicines. 2025 Jun 27;13(7):1576. doi: 10.3390/biomedicines13071576.
Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5-10% of all pregnancies and it is a leading cause of perinatal morbidity and mortality. During the initial phases of placentation, complex interlinked processes including cell proliferation, differentiation, apoptosis and the invasion of trophoblasts occur. Alterations in the regulation of these processes lead to placental dysfunction. Survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in cell proliferation balance and apoptosis, thus leading to proper placental development. This study aimed to evaluate survivin expression in placentas from IUGR and healthy pregnancies to explore its potential as a biomarker for the early diagnosis, prevention, and treatment of IUGR. : Survivin presence was determined in 153 archival formalin-fixed and paraffin-embedded placental tissues from IUGR (N = 122) and uncomplicated (N = 31) term pregnancies. Tissue microarrays (TMAs) were constructed, and survivin expression was assessed using immunohistochemistry (IHC). Survivin levels were quantified using positive cell proportion (PCP) scores and immunoreactive scores (IRS), with statistical significance determined using mean values, standard deviation (SD), standard error, and Student's t test in instances of normal distribution, and when this was not the case, the Mann-Whitney test. Chi-square tests, Fisher exact tests, and -tests ( < 0.05) were used to compare categorical variables. : Our results suggested the significantly higher expression of survivin validated with PCP ( < 0.001) and IRS ( < 0.002) in placentas with IUGR compared to placentas from non-complicated term pregnancies. : Increased survivin expression in IUGR placentas points to its potential role as a key indicator of placental dysfunction. By signaling early pathological changes, survivin may offer a valuable tool for the early detection of IUGR, potentially allowing for timely clinical interventions that could reduce the risk of serious outcomes, including stillbirth. To fully establish survivin's clinical value, further research is needed to validate its diagnostic accuracy and to explore its involvement in molecular pathways that may be targeted for therapeutic benefit.
宫内生长受限(IUGR)是一种病理状态,其定义为胎儿在妊娠期实现遗传预期生长潜能的能力降低。它影响所有妊娠的5%-10%,是围产期发病和死亡的主要原因。在胎盘形成的初始阶段,会发生包括细胞增殖、分化、凋亡和滋养层细胞侵袭在内的复杂相互关联的过程。这些过程调节的改变会导致胎盘功能障碍。生存素是凋亡抑制蛋白(IAP)家族的成员,在细胞增殖平衡和凋亡中起重要作用,从而导致胎盘正常发育。本研究旨在评估IUGR妊娠和正常妊娠胎盘组织中生存素的表达,以探索其作为IUGR早期诊断、预防和治疗生物标志物的潜力。:在153份存档的福尔马林固定石蜡包埋的胎盘组织中检测生存素的存在,这些胎盘组织来自IUGR妊娠(n=122)和无并发症的足月妊娠(n=31)。构建组织芯片(TMA),并使用免疫组织化学(IHC)评估生存素的表达。使用阳性细胞比例(PCP)评分和免疫反应评分(IRS)对生存素水平进行定量,在正态分布情况下,使用平均值、标准差(SD)、标准误和学生t检验确定统计学意义,若不满足正态分布,则使用曼-惠特尼检验。使用卡方检验、费舍尔精确检验和t检验(P<0.05)比较分类变量。:我们的结果表明,与无并发症的足月妊娠胎盘相比,IUGR胎盘组织中生存素的表达经PCP(P<0.001)和IRS(P<0.002)验证显著更高。:IUGR胎盘组织中生存素表达的增加表明其可能作为胎盘功能障碍的关键指标。通过提示早期病理变化,生存素可能为IUGR的早期检测提供有价值的工具,有可能实现及时的临床干预,从而降低包括死产在内的严重后果的风险。为了全面确立生存素的临床价值,需要进一步研究以验证其诊断准确性,并探索其在可能作为治疗靶点的分子途径中的作用。