Wang Xue, Li Xiaoqing, Yuan Shanshan, Gu Zhiju, An Zihao, Xu Qiang, Cao Bin, Song Yanhua, Tang Chao
National Clinical Research Center for Child Health, Children's Hospital Zhejiang University School of Medicine, Hangzhou, China.
Institute of Developmental Biology and Molecular Medicine, Fudan University, Shanghai, China.
Mol Med. 2025 May 23;31(1):202. doi: 10.1186/s10020-025-01268-5.
The proper distribution of nutrients and metabolites between the mother and fetus is one important factor for successful pregnancy. As a bridge, the placenta plays a key role in sensing the nutritional needs of the fetus, coordinating the maternal nutrition supply, and enhancing its nutritional transport capabilities. Imperfect placental development can lead to pregnancy-related disorders such as preeclampsia, recurrent miscarriage, and/or fetal growth restriction, posing risks to both mother and child in the short and long term. However, current understanding of the human placenta remains as a "black box", and its developmental control mechanisms for adaptive pregnant regulation still needs to be elucidated. As one form of post-translational modification (PTM), ubiquitination plays an important role in regulating cellular functions and is regarded as a valuable drug target. Particularly, ubiquitination related to placenta development has been discovered in recent years. Placental development processes closely associated with pregnant complications, such as blastocyst implantation, syncytiotrophoblast cell differentiation, and immune barrier maintenance, have been reported to be affected by ubiquitination. However, the diagnosis and intervention of pregnancy diseases also urgently need to be improved. Thus, aiming to comprehensive summarize and further exploring the molecular mechanism, target and regulatory mechanism of pregnancy complications, we have herein reviewed genes and pathways regulating pregnancy progress and diseases and focusing on ubiquitin-related physiological process in placenta.
母体与胎儿之间营养物质和代谢产物的合理分配是成功妊娠的一个重要因素。胎盘作为一座桥梁,在感知胎儿的营养需求、协调母体营养供应以及增强其营养转运能力方面发挥着关键作用。胎盘发育不完善会导致子痫前期、复发性流产和/或胎儿生长受限等妊娠相关疾病,无论短期还是长期,都会对母婴构成风险。然而,目前对人类胎盘的了解仍然如同一个“黑匣子”,其适应性妊娠调节的发育控制机制仍有待阐明。作为一种翻译后修饰(PTM)形式,泛素化在调节细胞功能中发挥着重要作用,并且被视为一个有价值的药物靶点。特别是,近年来已经发现了与胎盘发育相关的泛素化。据报道,与妊娠并发症密切相关的胎盘发育过程,如囊胚着床、合体滋养层细胞分化和免疫屏障维持,都受到泛素化的影响。然而,妊娠疾病的诊断和干预也迫切需要改进。因此,为了全面总结并进一步探索妊娠并发症的分子机制、靶点和调控机制,我们在此综述了调节妊娠进程和疾病的基因和途径,并重点关注胎盘中与泛素相关的生理过程。