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人胎盘和大鼠胎胎盘单位儿茶酚胺系统的发育表达。

Developmental expression of catecholamine system in the human placenta and rat fetoplacental unit.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Prague, Czech Republic.

出版信息

Sci Rep. 2024 Mar 23;14(1):6948. doi: 10.1038/s41598-024-57481-5.

Abstract

Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence has highlighted the importance of tightly regulated monoamine levels for placental functions and fetal development. However, the complexities of synthesis, release, and regulation of catecholamines in the fetoplacental unit have not been fully unraveled. In this study, we investigated the expression of enzymes and transporters involved in synthesis, degradation, and transport of norepinephrine and dopamine in the human placenta and rat fetoplacental unit. Quantitative PCR and Western blot analyses were performed in early-to-late gestation in humans (first trimester vs. term placenta) and mid-to-late gestation in rats (placenta and fetal brain, intestines, liver, lungs, and heart). In addition, we analyzed the gene expression patterns in isolated primary trophoblast cells from the human placenta and placenta-derived cell lines (HRP-1, BeWo, JEG-3). In both human and rat placentas, the study identifies the presence of only PNMT, COMT, and NET at the mRNA and protein levels, with the expression of PNMT and NET showing gestational age dependency. On the other hand, rat fetal tissues consistently express the catecholamine pathway genes, revealing distinct developmental expression patterns. Lastly, we report significant transcriptional profile variations in different placental cell models, emphasizing the importance of careful model selection for catecholamine metabolism/transport studies. Collectively, integrating findings from humans and rats enhances our understanding of the dynamic regulatory mechanisms that underlie catecholamine dynamics during pregnancy. We identified similar patterns in both species across gestation, suggesting conserved molecular mechanisms and potentially shedding light on shared biological processes influencing placental development.

摘要

儿茶酚胺去甲肾上腺素和多巴胺已被牵涉到中枢神经系统的许多生理过程中。新出现的证据强调了严格调节单胺水平对于胎盘功能和胎儿发育的重要性。然而,在胎-胎盘单位中儿茶酚胺的合成、释放和调节的复杂性尚未完全阐明。在这项研究中,我们研究了参与去甲肾上腺素和多巴胺合成、降解和转运的酶和转运体在人胎盘和大鼠胎-胎盘单位中的表达。在人类(早孕与足月胎盘)和大鼠(胎盘和胎儿脑、肠、肝、肺和心脏)的中晚期妊娠中进行了定量 PCR 和 Western blot 分析。此外,我们分析了从人胎盘分离的原代滋养层细胞和胎盘衍生细胞系(HRP-1、BeWo、JEG-3)中的基因表达模式。在人和大鼠的胎盘中,该研究鉴定出仅在 mRNA 和蛋白质水平上存在 PNMT、COMT 和 NET,PNMT 和 NET 的表达表现出妊娠年龄依赖性。另一方面,大鼠胎儿组织始终表达儿茶酚胺途径基因,显示出独特的发育表达模式。最后,我们报告了不同胎盘细胞模型中显著的转录谱变化,强调了在儿茶酚胺代谢/转运研究中仔细选择模型的重要性。综合来自人和大鼠的研究结果,增强了我们对妊娠期间儿茶酚胺动态的动态调节机制的理解。我们在整个妊娠过程中在两个物种中都发现了相似的模式,这表明存在保守的分子机制,并可能揭示影响胎盘发育的共享生物学过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f888/10960862/5f7968943187/41598_2024_57481_Fig1_HTML.jpg

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