The endocannabinoid anandamide impairs in vitro decidualization of human cells
The endocannabinoid anandamide impairs in vitro decidualization of human cells
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DOI：
10.1530/rep-16-0364
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发表时间：
2016-10-01
期刊：
影响因子：
3.8
通讯作者：
Fonseca, B. M.
中科院分区：
文献类型：
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作者：
Almada, M.;Amaral, C.;Fonseca, B. M.
内源性大麻素 (eCB) 是内源性介质，与大麻素受体（CB1 和 CB2）、膜转运蛋白和代谢酶一起形成内源性大麻素系统 (ECS)。已发现多种 eCB，重点是大麻素 (AEA)。它们参与多种生物过程，如能量平衡、免疫反应和繁殖。蜕膜化发生在人类月经周期的分泌期，涉及子宫内膜基质细胞增殖和分化为蜕膜细胞，对于妊娠的建立和进展至关重要。在本研究中，使用端粒酶永生化人子宫内膜基质细胞系 (St-T1b) 和来自足月胎盘的人蜕膜成纤维细胞的非分化原代培养物，通过免疫印迹和 qRT-PCR 技术来表征 ECS。结果表明，St-T1b 细胞表达 CB1，但不表达 CB2，并且这两种受体在 HdF 细胞中均表达。此外，脂肪酸酰胺水解酶（FAAH）（AEA的主要降解酶）的表达在基质细胞分化过程中增加。 AEA 通过放松细胞周期进程并诱导多倍体来抑制细胞增殖。此外，通过CB1结合受体，AEA还损害细胞分化。因此，AEA 被提议作为人类蜕膜化的调节剂。我们的研究结果可能会提供更广泛的影响，因为由于大麻消耗或代谢酶表达的改变而导致 AEA 水平失调，可能会对人类子宫内膜基质细胞蜕膜化产生负面调节，从而影响人类的生育能力。
Endocannabinoids (eCBs) are endogenous mediators that along with the cannabinoid receptors (CB1 and CB2), a membrane transporter and metabolic enzymes form the endocannabinoid system (ECS). Several eCBs have been discovered with emphasis on anandamide (AEA). They are involved in several biological processes such as energy balance, immune response and reproduction. Decidualization occurs during the secretory phase of human menstrual cycle, which involves proliferation and differentiation of endometrial stromal cells into decidual cells and is crucial for the establishment and progression of pregnancy. In this study, a telomerase-immortalized human endometrial stromal cell line (St-T1b) and non-differentiated primary cultures of human decidual fibroblasts from term placenta were used to characterize the ECS using immunoblotting and qRT-PCR techniques. It was shown that St-T1b cells express CB1, but not CB2, and that both receptors are expressed in HdF cells. Furthermore, the expression of fatty acid amide hydrolase (FAAH), the main degrading enzyme of AEA, increased during stromal cell differentiation. AEA inhibited cell proliferation, through deregulation of cell cycle progression and induced polyploidy. Moreover, through CB1 binding receptor, AEA also impaired cell differentiation. Therefore, AEA is proposed as a modulator of human decidualization. Our findings may provide wider implications, as deregulated levels of AEA, due to Cannabis sativa consumption or altered expression of the metabolic enzymes, may negatively regulate human endometrial stromal cell decidualization with an impact on human (in) fertility.