Abstract：
OBJECTIVE: Gestational diabetes mellitus (GDM) is one of the commonest medical complications of pregnancy. Annexin A5 (ANXA5) is a protein, found in apical surfaces of syncytiotrophoblasts, which prevents fetal and placental vascular thrombosis in GDM. Apelin is a bioactive peptide which has been linked to GDM. The aim of the present study was to correlate macroscopic as well as microscopic changes and immunohistochemical expression of ANXA5 and apelin in placentae of GDM with maternal and neonatal clinical features and also to compare the results with those in matched controls.
METHODS: This prospective observational study was undertaken for a period of one year from April 2020 to March 2021. It comprised of 42 patients of GDM. Gross features, microscopic features and intensity and grade of expression of ANXA5 and Apelin were analyzed in placentae of GDM.
RESULTS: Morphological changes detected in GDM placentae included increased immature villi (16 cases, 38%), increased syncytial knots (36, 86%), perivillous fibrin deposition (20, 48%), fibrosis of villous stroma (20, 48%), presence of nucleated red blood cells (12, 28.5%) and hypervascularity (34, 81%). The extent of histopathological changes noted in GDM placentae was significantly higher than that in matched controls. GDM placentae showed significantly reduced expression of ANXA5 and Apelin in terms of grade and intensity when compared with matched controls. Reduced expression (mild intensity) of ANXA5 was noted in 22 GDM cases (52.3%) whereas apelin expression was of weak intensity in 26 (61.9%) cases. Among GDM patients, statistically significant association was noted between ANXA5 intensity and neonatal resuscitation, apelin grade and preterm birth as well as low birth weight and apelin intensity and requirement of treatment in sick neonatal care unit.
CONCLUSIONS: The placental expression of the proteins, ANXA5 and Apelin, is altered in GDM though their exact pathogenetic mechanisms are yet to be understood. They can be targets for development of prophylactic and therapeutic agents in future.
METHODS: This prospective observational study was undertaken for a period of one year from April 2020 to March 2021. It comprised of 42 patients of GDM. Gross features, microscopic features and intensity and grade of expression of ANXA5 and Apelin were analyzed in placentae of GDM.
RESULTS: Morphological changes detected in GDM placentae included increased immature villi (16 cases, 38%), increased syncytial knots (36, 86%), perivillous fibrin deposition (20, 48%), fibrosis of villous stroma (20, 48%), presence of nucleated red blood cells (12, 28.5%) and hypervascularity (34, 81%). The extent of histopathological changes noted in GDM placentae was significantly higher than that in matched controls. GDM placentae showed significantly reduced expression of ANXA5 and Apelin in terms of grade and intensity when compared with matched controls. Reduced expression (mild intensity) of ANXA5 was noted in 22 GDM cases (52.3%) whereas apelin expression was of weak intensity in 26 (61.9%) cases. Among GDM patients, statistically significant association was noted between ANXA5 intensity and neonatal resuscitation, apelin grade and preterm birth as well as low birth weight and apelin intensity and requirement of treatment in sick neonatal care unit.
CONCLUSIONS: The placental expression of the proteins, ANXA5 and Apelin, is altered in GDM though their exact pathogenetic mechanisms are yet to be understood. They can be targets for development of prophylactic and therapeutic agents in future.
摘要：
目的：妊娠期糖尿病（GDM）是妊娠期最常见的内科并发症之一。膜联蛋白A5（ANXA5）是一种蛋白质，在合胞体滋养层的顶端表面发现，预防GDM中胎儿和胎盘血管血栓形成。Apelin是已与GDM连接的生物活性肽。本研究的目的是将GDM胎盘中ANXA5和apelin的宏观和微观变化以及免疫组织化学表达与母体和新生儿的临床特征相关联，并将结果与匹配的对照组进行比较。
方法：这项前瞻性观察性研究从2020年4月至2021年3月进行了为期一年的研究。它包括42名GDM患者。总特征,分析了GDM胎盘中ANXA5和Apelin的显微特征以及表达强度和等级。
结果：在GDM胎盘中检测到的形态变化包括未成熟绒毛增加（16例，38%），合胞结增加（36，86%），绒毛周围纤维蛋白沉积（20，48%），绒毛间质纤维化（20，48%），有核红细胞（12，28.5％）和高血管（34，81％）的存在。GDM胎盘的组织病理学变化程度显着高于匹配的对照组。与匹配的对照相比，GDM胎盘在等级和强度方面显示ANXA5和Apelin的表达显着降低。在22例GDM病例（52.3％）中，ANXA5的表达降低（轻度强度），而在26例（61.9％）中，apelin的表达强度较弱。在GDM患者中，ANXA5强度与新生儿复苏之间存在统计学上的显着关联，apelin分级和早产以及低出生体重和apelin强度和生病新生儿监护病房的治疗需求。
结论：胎盘蛋白的表达，ANXA5和Apelin，在GDM中发生了改变，尽管它们的确切致病机制尚待了解。它们可以成为将来开发预防剂和治疗剂的靶标。
方法：这项前瞻性观察性研究从2020年4月至2021年3月进行了为期一年的研究。它包括42名GDM患者。总特征,分析了GDM胎盘中ANXA5和Apelin的显微特征以及表达强度和等级。
结果：在GDM胎盘中检测到的形态变化包括未成熟绒毛增加（16例，38%），合胞结增加（36，86%），绒毛周围纤维蛋白沉积（20，48%），绒毛间质纤维化（20，48%），有核红细胞（12，28.5％）和高血管（34，81％）的存在。GDM胎盘的组织病理学变化程度显着高于匹配的对照组。与匹配的对照相比，GDM胎盘在等级和强度方面显示ANXA5和Apelin的表达显着降低。在22例GDM病例（52.3％）中，ANXA5的表达降低（轻度强度），而在26例（61.9％）中，apelin的表达强度较弱。在GDM患者中，ANXA5强度与新生儿复苏之间存在统计学上的显着关联，apelin分级和早产以及低出生体重和apelin强度和生病新生儿监护病房的治疗需求。
结论：胎盘蛋白的表达，ANXA5和Apelin，在GDM中发生了改变，尽管它们的确切致病机制尚待了解。它们可以成为将来开发预防剂和治疗剂的靶标。
