Changes of Phospholipids in Fetal Liver of Mice Conceived by In Vitro Fertilization1
Changes of Phospholipids in Fetal Liver of Mice Conceived by In Vitro Fertilization1
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DOI：
10.1095/biolreprod.115.136325
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Bo Li;Xi-feng Xiao;Shuqiang Chen;Jianlei Huang;Ye-fei Ma;Na Tang;Huijun Sun;Xiaohong Wang
中科院分区：
文献类型：
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作者：
Bo Li;Xi-feng Xiao;Shuqiang Chen;Jianlei Huang;Ye-fei Ma;Na Tang;Huijun Sun;Xiaohong Wang
发育早期的环境影响增加了成年期代谢性疾病的易感性。辅助生殖技术（ART）将配子或植入前胚胎暴露在非生理环境中，增加了晚年患代谢疾病的风险。然而，ART相关代谢疾病的确切潜在原因仍不清楚。在我们之前的研究中，通过使用小鼠模型，我们发现ART导致胎盘发育不良和功能障碍，导致胎儿生长减少。胎盘中的脂质代谢和脂质转运蛋白也受到ART的影响。基于这些发现，我们假设ART可能会阻碍胎儿的脂质代谢，这可能会导致日后代谢性疾病的发生。在本研究中，通过脂质组学分析，我们首次研究了ART对小鼠模型胎肝磷脂谱的影响，并对其进行了详细概述。我们发现，ART显着增加溶血磷脂酰胆碱（LPC），磷脂酸（PA），溶血磷脂酰乙醇胺在胎儿的肝脏与对照组相比。LPC和PA作为信号分子参与大多数细胞过程，调节许多重要的生理和病理生理过程。LPC已被证明在动脉粥样硬化和2型糖尿病的发展中起着至关重要的作用，PA的增加可导致胰岛素抵抗。提示LPC和PA的变化可能是ART小鼠糖代谢改变和血管功能障碍的原因之一。
ABSTRACT Environmental influences during early development increase the susceptibility to metabolism diseases in adulthood. Assisted reproductive techniques (ART) expose the gametes or preimplantation embryo to a nonphysiological environment that increases the risk of metabolism diseases in later life. However, the precise underlying causes of ART-related metabolism disease remain unclear. In our previous study, by using a mouse model, we found that ART resulted in placental maldevelopment and dysfunction that led to reduced fetal growth. The lipid metabolism and lipid transporters in the placenta were also affected by ART. Based on these findings, we hypothesized that ART may hamper fetal lipid metabolism, which could predispose to metabolic diseases in later life. In the present examination, by lipidomic analysis, we investigated for the first time the effect of ART on phospholipid profiles in the fetal liver in a mouse model and presented it in a detailed overview. We revealed that ART increased significantly the level of lysophosphatidylcholine (LPC), phosphatidic acid (PA), and lysophosphatidylethanolamine in the livers of fetuses compared with those in the controls. LPC and PA acts as signaling molecules involved in the majority of cellular processes regulating many crucial physiological and pathophysiological processes. LPC has been shown to play a crucial role in the development of atherosclerosis and type 2 diabetes, and an increase in PA can result in insulin resistance. We proposed that changes of LPC and PA may be one of the causes of the changes in glucose metabolism and vascular dysfunction in the mouse model of ART.