Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.

藁本内酯（LIG）是当归的主要活性成分(Oliv.) Diels，它可以促进局部血管生成以发挥神经保护作用。然而，目前还没有报道证实LIG对子宫内膜血管生成和妊娠结局的确切影响。为了探讨LIG对低子宫内膜容受性（LER）和血管生成的影响，将妊娠大鼠分为对照组（盐水治疗）、LER（羟基脲-肾上腺素治疗）、LIG 20 mg/kg组和LIG 40 mg/kg组。进行苏木精和伊红 (H&E) 染色以评估子宫内膜形态。分别采用实时定量PCR、免疫荧光染色、蛋白质印迹和免疫组织化学染色评估子宫内膜容受因子和血管生成相关基因/蛋白的表达。采用RNA测序分析LIG对肾虚血瘀引起的LER的影响。我们发现羟基脲肾上腺素治疗的妊娠大鼠的子宫内膜厚度和植入的胚胎数量显着减少。同时，LER组子宫内膜中ERα、LIF、VEGFA、CD31基因及蛋白表达量显着降低，MUC1、E-cadherin表达量升高。LIG 的施用增加了子宫内膜厚度和植入的胚胎，并逆转了这些因子的表达。总的来说，我们的研究结果表明，LIG 可以通过恢复子宫内膜容受性和促进子宫内膜血管生成来促进胚胎植入。LER组子宫内膜VEGFA、CD31表达明显减少，MUC1、E-cadherin表达增加。LIG 的施用增加了子宫内膜厚度和植入的胚胎，并逆转了这些因子的表达。总的来说，我们的研究结果表明，LIG 可以通过恢复子宫内膜容受性和促进子宫内膜血管生成来促进胚胎植入。LER组子宫内膜VEGFA、CD31表达明显减少，MUC1、E-cadherin表达增加。LIG 的施用增加了子宫内膜厚度和植入的胚胎，并逆转了这些因子的表达。总的来说，我们的研究结果表明，LIG 可以通过恢复子宫内膜容受性和促进子宫内膜血管生成来促进胚胎植入。