CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Ph.D. Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
Department of Obstetrics and Gynecology, Medical University of Graz, 8063 Graz, Austria; Research Unit Early Life Determinants (ELiD), Medical University of Graz, 8036 Graz, Austria.
Biochim Biophys Acta Mol Basis Dis. 2023 Dec;1869(8):166834. doi: 10.1016/j.bbadis.2023.166834. Epub 2023 Aug 2.
Gestational diabetes mellitus (GDM) and maternal obesity (MO) increase the risk of adverse fetal outcomes, and the incidence of cardiovascular disease later in life. Extensive research has been conducted to elucidate the underlying mechanisms by which GDM and MO program the offspring to disease. This review focuses on the role of fetoplacental endothelial dysfunction in programming the offspring for cardiovascular disease in GDM and MO pregnancies. We discuss how pre-existing maternal health conditions can lead to vascular dysfunction in the fetoplacental unit and the fetus. We also examine the role of fetoplacental endothelial dysfunction in impairing fetal cardiovascular system development and the involvement of nitric oxide and hydrogen sulfide in mediating fetoplacental vascular dysfunction. Furthermore, we suggest that the L-Arginine-Nitric Oxide and the Adenosine-L-Arginine-Nitric Oxide (ALANO) signaling pathways are pertinent targets for research. Despite significant progress in this area, there are still knowledge gaps that need to be addressed in future research.
妊娠期糖尿病(GDM)和母体肥胖(MO)增加了不良胎儿结局的风险,并增加了日后发生心血管疾病的风险。大量研究旨在阐明 GDM 和 MO 使后代易患疾病的潜在机制。本综述重点关注胎盘中皮功能障碍在 GDM 和 MO 妊娠中为后代心血管疾病编程的作用。我们讨论了先前存在的母体健康状况如何导致胎盘中皮功能障碍以及胎儿的血管功能障碍。我们还研究了胎盘中皮功能障碍在损害胎儿心血管系统发育中的作用,以及一氧化氮和硫化氢在介导胎盘中皮血管功能障碍中的作用。此外,我们认为 L-精氨酸-一氧化氮和腺苷-L-精氨酸-一氧化氮(ALANO)信号通路是相关的研究靶点。尽管在这一领域取得了重大进展,但仍有一些知识空白需要在未来的研究中解决。