Evidence for functional interactions between the placenta and brain in pregnant mice
Evidence for functional interactions between the placenta and brain in pregnant mice
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DOI：
10.1096/fj.201802037r
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发表时间：
2019-03-01
期刊：
影响因子：
4.8
通讯作者：
Spencer, Thomas E.
中科院分区：
文献类型：
--
作者：
Behura, Susanta K.;Kelleher, Andrew M.;Spencer, Thomas E.
胎盘在胎儿大脑发育中起着举足轻重的作用，也影响着母体的大脑功能，但我们对胎盘与大脑之间的联系的了解仍然有限。利用基因表达和网络分析的方法，我们提供了胎盘转录组与妊娠15天的C57BL/6J小鼠母脑和胎脑紧密相连的证据。5-羟色胺能突触信号的激活和神经营养素信号的抑制分别被认为是胎盘与母脑和胎儿脑之间串扰的潜在中介。编码特定受体和配体的基因被预测会影响胎盘和大脑之间的功能相互作用。具有4个MBT结构域的中腿同源性梳1/SCM样基因和多梳环指(Pcgf)2/Pcgf5等相似基因在胎盘和脑之间表现出拮抗调节。此外，有条件地切除子宫腺体中的叉头盒a2(Foxa2)改变了d15胎盘的转录组，这为子宫腺和胎盘之间的串扰提供了新的证据。此外，Foxa2条件性基因敲除小鼠胎脑组织蛋白酶6和单核巨噬细胞分化相关基因2的表达与对照组相比有显著差异。这些发现有助于更好地理解怀孕期间子宫-胎盘-大脑相互作用的复杂性，并为他们的探索提供了一个基础和模型系统。
The placenta plays a pivotal role in the development of the fetal brain and also influences maternal brain function, but our understanding of communication between the placenta and brain remains limited. Using a gene expression and network analysis approach, we provide evidence that the placenta transcriptome is tightly interconnected with the maternal brain and fetal brain in d 15 pregnant C57BL/6J mice. Activation of serotonergic synapse signaling and inhibition of neurotrophin signaling were identified as potential mediators of crosstalk between the placenta and maternal brain and fetal brain, respectively. Genes encoding specific receptors and ligands were predicted to affect functional interactions between the placenta and brain. Paralogous genes, such as sex comb on midleg homolog 1/scm-like with 4 mbt domains 2 and polycomb group ring finger (Pcgf) 2/Pcgf5, displayed antagonistic regulation between the placenta and brain. Additionally, conditional ablation of forkhead box a2 (Foxa2) in the glands of the uterus altered the transcriptome of the d 15 placenta, which provides novel evidence of crosstalk between the uterine glands and placenta. Furthermore, expression of cathepsin 6 and monocyte to macrophage differentiation associated 2 was significantly different in the fetal brain of Foxa2 conditional knockout mice compared with control mice. These findings provide a better understanding of the intricacies of uterus-placenta-brain interactions during pregnancy and provide a foundation and model system for their exploration.Behura, S. K., Kelleher, A. M., Spencer, T. E. Evidence for functional interactions between the placenta and brain in pregnant mice.