Placental Changes in the serotonin transporter (Slc6a4) knockout mouse suggest a role for serotonin in controlling nutrient acquisition.
Placental Changes in the serotonin transporter (Slc6a4) knockout mouse suggest a role for serotonin in controlling nutrient acquisition.
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DOI：
10.1016/j.placenta.2021.09.021
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发表时间：
2021-11
期刊：
影响因子：
3.8
通讯作者：
Rosenfeld CS
中科院分区：
文献类型：
--
作者：
Mao J;Kinkade JA;Bivens NJ;Roberts RM;Rosenfeld CS
小鼠胎盘在胎盘和母体蜕膜交界处的壁层滋养层巨细胞(PTGC)中积聚并可能产生5-羟色胺(5-羟色胺；5-羟色胺)。然而，5-羟色胺在胎盘功能中的作用尚不清楚。这种信息的缺乏是不幸的，因为选择性5-羟色胺再摄取抑制剂通常被用来对抗孕妇的抑郁。高亲和力的5-羟色胺转运体SLC6A4(也称为SERT)是这类药物的靶标，可能控制pTGC和其他胎盘细胞对5-羟色胺的摄取。我们推测，去除SLC6A4基因将导致与胎盘基因表达变化相关的形态变化，特别是那些参与营养获取和代谢的基因，从而为深入了解5-羟色胺的胎盘功能提供依据。胎龄12.5的胎盘来自SLC6A4基因敲除(KO)和野生型(WT)胚胎。进行组织学、RNAseq、qPCR和综合相关分析。与WT胎盘相比，SLC6A4 KO胎盘的pTGC/海绵滋养细胞面积比显著增加，与肠道功能相关的基因表达显著增加，包括营养感知、摄取、分解代谢和凝血。综合相关分析表明，其中许多基因的上调与pTGC层扩展有关。另一个关键基因是多巴脱羧酶，它催化L-5-羟色氨酸转化为5-羟色氨酸。我们的研究可能提出了一种新的范式，与5-羟色胺在胎盘中的作用有关，即作为一种调节代谢功能和凝血的因子。我们进一步认为，pTGC可能是肠粘膜5-羟色胺阳性细胞的功能类似物，它们调节肠道内的类似活动。需要进一步的工作，包括蛋白质组学和代谢组学研究，以支持我们的假设。
The mouse placenta accumulates and possibly produces serotonin (5-hydroxytryptamine; 5-HT) in parietal trophoblast giant cells (pTGC) located at the interface between the placenta and maternal deciduum. However, the roles of 5-HT in placental function are unclear. This lack of information is unfortunate, given that selective serotonin-reuptake inhibitors are commonly used to combat depression in pregnant women. The high affinity 5-HT transporter SLC6A4 (also known as SERT) is the target of such drugs and likely controls much of 5-HT uptake into pTGC and other placental cells. We hypothesized that ablation of the Slc6a4 gene would result in morphological changes correlated with placental gene expression changes, especially for those involved in nutrient acquisition and metabolism, and thereby, provide insights into 5-HT placental function. Placentas were collected at embryonic age (E) 12.5 from Slc6a4 knockout (KO) and wild-type (WT) conceptuses. Histological, RNAseq, qPCR, and integrative correlation analyses were performed. Slc6a4 KO placentas had a considerable increased pTGC to spongiotrophoblast area ratio relative to WT placentas and significantly elevated expression of genes associated with intestinal functions, including nutrient sensing, uptake, and catabolism, and blood clotting. Integrative correlation analyses revealed upregulation of many of these genes was correlated with pTGC layer expansion. One other key gene was dopa decarboxylase (Ddc), which catalyzes conversion of L-5-hydroxytryptophan to 5-HT. Our studies possibly suggest a new paradigm relating to how 5-HT operates in the placenta, namely as a factor regulating metabolic functions and blood coagulation. We further suggest that pTGC might be functional analogs of enterochromaffin 5-HT-positive cells of the intestinal mucosa, which regulate similar activities within the gut. Further work, including proteomics and metabolomic studies, are needed to buttress our hypothesis.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
5.4
作者：
Horackova H;Karahoda R;Cerveny L;Vachalova V;Ebner R;Abad C;Staud F
通讯作者：
Staud F
DOI：
10.1073/pnas.0800466105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Baganz, Nicole L.;Horton, Rebecca E.;Daws, Lynette C.
通讯作者：
Daws, Lynette C.
影响因子：
4.8
作者：
Kliman，Harvey J.;Quaratella，Sarah B.;Steck，Theodore L.
通讯作者：
Steck，Theodore L.
影响因子：
3.8
作者：
Klempan, T.;Hudon-Thibeault, A. -A.;Sanderson, J. T.
通讯作者：
Sanderson, J. T.