Unique Ultrastructural Alterations in the Placenta Associated With Macrosomia Induced by Gestational Diabetes Mellitus

Abstract Objective To investigate the morphological and ultrastructural alterations in placentas from pregnancies with gestational diabetes mellitus (GDM)–induced macrosomia, term nondiabetic macrosomia, and normal pregnancies. Methods Sixty full-term placentas were collected, and clinical data along with informed consent were obtained from pregnant women who underwent regular visit checks and delivered their newborns in Northwest Women’s and Children’s Hospital between May and December 2022. Placentas were divided into three equal groups: normal pregnancy (control group), nondiabetic macrosomia group, and macrosomia complicated with GDM (diabetic macrosomia) group. Gross morphological data of placentas were recorded, and placental samples were processed for examination of ultrastructural and stereological changes using transmission electron microscopy. Analysis of variance and chi-squared test were used to examine the differences among the three groups for continuous and categorical variables, respectively. Results The baseline characteristics of mothers and neonates did not differ across the three groups, except for a significantly higher birth weight in the diabetic macrosomia group (4172.00 ± 151.20 g vs . 3192.00 ± 328.70 g, P < 0.001) and nondiabetic macrosomia group (4138.00 ± 115.20 g vs. 3192.00 ± 328.70 g, P < 0.001) compared with control group. Examination of the placentas revealed that placental weight was also highest in the diabetic macrosomia group compared with control group (810.00 ± 15.81 g vs. 490.00 ± 51.48 g, P < 0.001) and nondiabetic macrosomia group (810.00 ± 15.81 g vs. 684.00 ± 62.69 g, P < 0.001), but the ratio of neonatal birth weight to placental weight (BW/PW) was significantly lower in the diabetic macrosomia group compared with that in the control group (5.15 ± 0.19 vs. 6.54 ± 0.63, P < 0.001) and nondiabetic macrosomia group (5.15 ± 0.19 vs. 6.09 ± 0.52, P < 0.001) group. In contrast, the BW/PW ratio in nondiabetic macrosomia did not differ significantly from that in the control group. Distinct ultrastructural changes in terminal villi and stereological alterations in microvilli were observed in the diabetic macrosomia group, including changes in the appearance of cytoplasmic organelles and the fetal capillary endothelium and thickness of the vasculo-syncytial membrane and basal membrane. Conclusion Significant ultrastructural and stereological alterations were discovered in the placentas from pregnant women with macrosomia induced by GDM. These alterations may be the response of the placenta to the hyperglycemia condition encountered during pregnancies complicated with GDM.