Biomedical Sciences, University of Missouri, Columbia, MO, USA.
Division of Animal Sciences, University of Missouri, Columbia, MO, USA.
Biol Reprod. 2024 Feb 10;110(2):310-328. doi: 10.1093/biolre/ioad146.
The fetal brain of the mouse is thought to be dependent upon the placenta as a source of serotonin (5-hydroxytryptamine; 5-HT) and other factors. How factors reach the developing brain remains uncertain but are postulated here to be part of the cargo carried by placental extracellular vesicles (EV). We have analyzed the protein, catecholamine, and small RNA content of EV from mouse trophoblast stem cells (TSC) and TSC differentiated into parietal trophoblast giant cells (pTGC), potential primary purveyors of 5-HT. Current studies examined how exposure of mouse neural progenitor cells (NPC) to EV from either TSC or pTGC affect their transcriptome profiles. The EV from trophoblast cells contained relatively high amounts of 5-HT, as well as dopamine and norepinephrine, but there were no significant differences between EV derived from pTGC and from TSC. Content of miRNA and small nucleolar (sno)RNA, however, did differ according to EV source, and snoRNA were upregulated in EV from pTGC. The primary inferred targets of the microRNA (miRNA) from both pTGC and TSC were mRNA enriched in the fetal brain. NPC readily internalized EV, leading to changes in their transcriptome profiles. Transcripts regulated were mainly ones enriched in neural tissues. The transcripts in EV-treated NPC that demonstrated a likely complementarity with miRNA in EV were mainly up- rather than downregulated, with functions linked to neuronal processes. Our results are consistent with placenta-derived EV providing direct support for fetal brain development and being an integral part of the placenta-brain axis.
人们认为，老鼠的胎儿大脑依赖于胎盘作为 5-羟色胺（5-HT）和其他因素的来源。这些因素如何到达发育中的大脑尚不清楚，但据推测，它们是胎盘细胞外囊泡（EV）携带的一部分货物。我们分析了来自鼠滋养层干细胞（TSC）和分化为壁层滋养层巨大细胞（pTGC）的 EV 的蛋白质、儿茶酚胺和小 RNA 含量，pTGC 是 5-HT 的潜在主要供应者。目前的研究检查了暴露于来自 TSC 或 pTGC 的 EV 的鼠神经祖细胞（NPC）如何影响它们的转录组谱。滋养层细胞的 EV 含有相对较高水平的 5-HT、多巴胺和去甲肾上腺素，但 pTGC 和 TSC 衍生的 EV 之间没有显着差异。然而，根据 EV 的来源，miRNA 和小核仁（sno）RNA 的含量存在差异，并且 snoRNA 在 pTGC 的 EV 中上调。来自 pTGC 和 TSC 的 miRNA 的主要推断靶标是富含胎儿大脑的 mRNA。NPC 容易内化 EV，导致其转录组谱发生变化。受调控的转录本主要是富含神经组织的转录本。在 EV 处理的 NPC 中，与 EV 中的 miRNA 具有互补性的转录本主要是上调而不是下调，其功能与神经元过程有关。我们的结果表明，胎盘衍生的 EV 为胎儿大脑发育提供直接支持，并成为胎盘-大脑轴的一个组成部分。
