Huang Yun, Ni Yanyan, Meng Yu, Zeng Xiaojing, He Xiaoqing, Zhang Lin, Zhang Jun
Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
BMC Pregnancy Childbirth. 2024 Dec 26;24(1):868. doi: 10.1186/s12884-024-07097-4.
Delivery mode has been linked to child health, e.g., allergic disease. However, it remains unclear whether protein and metabolite differences across different delivery modes may underlie child development.
A cohort comprising 16 spontaneous onset vaginal delivery (VD), 16 prelabor cesarean delivery on maternal request (CS), and 8 intrapartum cesarean section (Intra_CS) women were analyzed using label-free proteomic and untargeted metabolomics assays on amniotic fluid and cord blood samples, respectively. We used weighted gene co-expression network analyses (WGCNA) to identify modules of highly correlated proteins or metabolites that associated with delivery modes and related clinical traits. KEGG enrichment analyses were performed to investigate the biological function of the identified modules. Integrative multiomics analysis was employed to examine the biological interplay between proteomic and metabolic interactions.
Compared to the CS group, the proteomic and metabolomic profiles were similar between the Intra_CS and VD groups in our study. We did not identify any enriched protein or metabolite pathways related to immune development that could influence the risk of allergic diseases in offspring across different delivery modes. However, we identified seven protein modules correlated with the duration from the rupture of the membranes to full dilation of the cervix, with the actin cytoskeleton module significantly enriched. A metabolic module in cord blood that correlated with VD was enriched in subclasses including C21 steroids, steroid sulfates, and oxysterols. Integrative analysis of proteomic and metabolomic data suggested pathways related to mode of delivery and duration of labor, encompassing the actin cytoskeleton, NADP metabolic process, nicotinate, and nicotinamide metabolism in amniotic fluid, and the steroid hormone biosynthesis pathway in cord blood.
Differences in steroid hormones and the actin cytoskeleton pathway according to proteomics and metabolomics in amniotic fluid and cord blood were more indicative of the labor process. These findings could guide future studies on delivery-associated biochemical pathways.
分娩方式与儿童健康相关，例如与过敏性疾病有关。然而，不同分娩方式下蛋白质和代谢物的差异是否可能是儿童发育的基础仍不清楚。
分别对羊水和脐带血样本进行无标记蛋白质组学和非靶向代谢组学分析，分析了一个队列，该队列包括16例自然发动的阴道分娩（VD）、16例因产妇要求进行的临产前剖宫产（CS）和8例产时剖宫产（Intra_CS）的女性。我们使用加权基因共表达网络分析（WGCNA）来识别与分娩方式和相关临床特征相关的高度相关蛋白质或代谢物模块。进行KEGG富集分析以研究已识别模块的生物学功能。采用综合多组学分析来检查蛋白质组学和代谢相互作用之间的生物学相互作用。
在我们的研究中，与CS组相比，Intra_CS组和VD组的蛋白质组学和代谢组学特征相似。我们没有发现任何与免疫发育相关的富集蛋白质或代谢物途径，这些途径可能会影响不同分娩方式下后代患过敏性疾病的风险。然而，我们确定了七个与胎膜破裂至宫颈完全扩张的持续时间相关的蛋白质模块，其中肌动蛋白细胞骨架模块显著富集。脐带血中与VD相关的一个代谢模块在包括C21类固醇、类固醇硫酸盐和氧甾醇在内的亚类中富集。蛋白质组学和代谢组学数据的综合分析表明，与分娩方式和产程持续时间相关的途径包括羊水内的肌动蛋白细胞骨架、NADP代谢过程、烟酸和烟酰胺代谢，以及脐带血中的类固醇激素生物合成途径。
羊水和脐带血中蛋白质组学和代谢组学显示的类固醇激素和肌动蛋白细胞骨架途径的差异更能反映产程情况。这些发现可为未来与分娩相关的生化途径研究提供指导。
