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首页> 外文期刊>Journal of biochemical and molecular toxicology >GABA consumption during early pregnancy impairs endometrial receptivity and embryo development in mice
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GABA consumption during early pregnancy impairs endometrial receptivity and embryo development in mice

机译：妊娠早期的GABA消费损害小鼠的子宫内膜接受和胚胎发育

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摘要

γ-Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity-related factors—LIF, E-cadherin, and HOXA10— were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50μg/μL) markedly inhibited preimplantation embryo development in a dose-response manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40μM 2-hydroxysaclofen, a GABA_B antagonist, indicating that GABA exerts its inhibitory effects via its B-type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B-type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy.
机译：γ-氨基丁酸（GABA）因其在缓解压力、缓解焦虑和改善睡眠方面的积极作用，被年轻女性普遍用作食品补充剂和保健品。然而，它在不同产品中的推荐日剂量差异很大。此外，尚不清楚妊娠早期GABA的摄入是否以及如何影响妊娠的建立。在这项研究中，我们发现，当妊娠小鼠在植入前（口服）高剂量（12.5 mg/g）GABA时，妊娠第5天的植入部位数量减少。此外，在这些未移植的胚胎中，大多数表现出形态退化和发育迟缓，只有少数胚胎发育成囊胚，但无法植入子宫。此外，子宫容受性相关因子LIF、E-钙粘蛋白和HOXA10-的表达均下调，而高GABA剂量组的子宫腺体数量减少。最后，体外实验结果表明，GABA（范围为10至50μg/μL）以剂量反应方式显著抑制着床前胚胎发育。然而，当用GABA_B拮抗剂40μM 2-羟基沙氯芬预处理胚胎时，未观察到这种抑制作用，这表明GABA通过其B型受体发挥抑制作用。我们的结果表明，在妊娠早期，暴露于一定浓度的GABA可通过其B型受体损害着床前胚胎的发育，并损害子宫内膜的容受性，从而严重干扰小鼠的早期胚胎着床。这些发现可能会引起人们对妊娠早期GABA摄入的担忧。

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