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首页> 外文期刊>Human Reproduction >High levels of anandamide, an endogenous cannabinoid, block the growth of sheep preimplantation embryos by inducing apoptosis and reversible arrest of cell proliferation.
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High levels of anandamide, an endogenous cannabinoid, block the growth of sheep preimplantation embryos by inducing apoptosis and reversible arrest of cell proliferation.

机译：高水平的anandamide（一种内源性大麻素）可通过诱导凋亡和细胞增殖的可逆性阻滞来阻止绵羊植入前胚胎的生长。

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摘要

BACKGROUND: The process of implantation is mediated by various molecules, one of which is anandamide (AEA), a lipid signalling ligand belonging to the family of endocannabinoids. AEA exerts its effects on implantation by binding to the Type 1 Cannabinoid Receptor (CB1-R), expressed in both blastocysts and uterus. We wanted to know whether the endocannabinoid signalling system was present also in the sheep reproductive tract and which kind of effect(s) AEA had on the development of sheep blastocysts in vitro. METHODS: We analysed the expression and activity of the endocannabinoid system in sheep reproductive tracts and blastocysts. Hatched sheep blastocysts were then exposed to AEA and its effect(s) were determined by TUNEL assay and by measuring the rate of necrosis and 5-bromo-deoxyuridine incorporation. RESULTS: We show that the AEA signalling system is present in sheep and that high concentrations of AEA induce apoptosis and inhibit cell proliferation via a CB1-R-dependent mechanism. Indeed, AEA effects were blocked when sheep blastocysts were cultured in the presence of the CB1-R antagonist SR161417A. Moreover, AEA inhibition of cell proliferation was reversible, as arrested embryos resumed a normal growth rate upon AEA removal from the medium. CONCLUSIONS: Our results suggest that disturbed regulation of AEA signalling via CB1-R may be associated with pregnancy failure. AEA could lower the quality of blastocysts by inducing apoptosis and inhibiting cell proliferation, thus making them incompetent for implantation.
机译：背景：植入过程是由各种分子介导的，其中之一是Anandamide（AEA），这是一种内源性大麻素家族的脂质信号配体。 AEA通过结合在胚泡和子宫中表达的1型大麻素受体（CB1-R）发挥其对植入的作用。我们想知道绵羊生殖道中是否也存在内源性大麻素信号传导系统，以及AEA在体外对绵羊胚泡的发育有何作用。方法：我们分析了内源性大麻素系统在绵羊生殖道和囊胚中的表达和活性。然后将孵化的绵羊胚泡暴露于AEA中，并通过TUNEL分析并通过测量坏死率和5-溴-脱氧尿苷掺入来确定其作用。结果：我们表明绵羊中存在AEA信号系统，并且高浓度的AEA通过CB1-R依赖性机制诱导细胞凋亡并抑制细胞增殖。实际上，当在CB1-R拮抗剂SR161417A存在的情况下培养绵羊胚泡时，AEA的作用被阻断。此外，AEA对细胞增殖的抑制作用是可逆的，因为从培养基中去除AEA后，被捕胚胎恢复了正常的生长速度。结论：我们的结果表明，通过CB1-R干扰AEA信号调节可能与妊娠失败有关。 AEA可能通过诱导凋亡和抑制细胞增殖而降低胚泡的质量，从而使其无法植入。

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