Luo Lan, Luo Man, Ning Donghong, Chen Xi, Zheng Qiuman, Cao Qin
Department of TCM Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Hunan 410008, P.R. China.
Hunan University of Chinese Medicine, Hunan 410208, P.R. China.
J Reprod Dev. 2025 Jun 6;71(3):161-167. doi: 10.1262/jrd.2024-096. Epub 2025 Apr 28.
A thin endometrium can lead to low clinical pregnancy rates, low live birth rates, high spontaneous abortion rates, and low birth weight. However, current methods of treating thin endometria do not achieve ideal results. This study explored the effect of Indian Hedgehog (IHH) on thin endometrium and its mechanism of action. A thin endometrial rat model was established by infusion of 95% ethanol. IHH was overexpressed in model rats using adeno-associated viruses. The endometrial thickness and number of glands and vessels were determined using H&E staining. Endometrial fibrosis was detected using Masson's trichrome staining. Immunohistochemistry was performed to detect α-SMA, MUC-1, and CK19. After modeling, the rats were mated, and the number of gestational sacs was counted for fertility assessment. Western blotting was used to detect the angiogenesis markers vWF, PCNA, and vim and Hedgehog signaling-related proteins SMO, GLI1, and GLI3. IHH overexpression reduced ethanol-induced edema and bruising, repaired the appearance of damaged tissue, increased endometrial thickness, promoted glandular and vascular regeneration, and alleviated endometrial fibrosis. IHH overexpression inhibited the expression of fibroblast marker α-SMA while promoting the expression of vWF, PCNA, vim, CK19, and MUC-1. It also increased the number of gestational sacs and promoted the expression of SMO, GLI1, and GLI3. In conclusion, IHH ameliorates ethanol-induced thin endometrium and improves fertility by activating the Hedgehog signaling pathway.
薄型子宫内膜可导致临床妊娠率低、活产率低、自然流产率高和低出生体重。然而,目前治疗薄型子宫内膜的方法并未取得理想效果。本研究探讨了印度刺猬因子(IHH)对薄型子宫内膜的作用及其作用机制。通过注入95%乙醇建立薄型子宫内膜大鼠模型。使用腺相关病毒在模型大鼠中过表达IHH。采用苏木精-伊红(H&E)染色测定子宫内膜厚度、腺体和血管数量。采用Masson三色染色检测子宫内膜纤维化。进行免疫组织化学检测α-平滑肌肌动蛋白(α-SMA)、粘蛋白1(MUC-1)和细胞角蛋白19(CK19)。建模后,将大鼠进行交配,并计算妊娠囊数量以评估生育能力。采用蛋白质免疫印迹法检测血管生成标志物血管性血友病因子(vWF)、增殖细胞核抗原(PCNA)和波形蛋白(vim)以及刺猬信号相关蛋白 smoothened(SMO)、glioma-associated oncogene homolog 1(GLI1)和glioma-associated oncogene homolog 3(GLI3)。IHH过表达减少了乙醇诱导的水肿和瘀伤,修复了受损组织外观,增加了子宫内膜厚度,促进了腺体和血管再生,并减轻了子宫内膜纤维化。IHH过表达抑制成纤维细胞标志物α-SMA的表达,同时促进vWF、PCNA、vim 和 CK19以及MUC-1的表达。它还增加了妊娠囊数量,并促进了SMO、GLI1和GLI3的表达。总之,IHH通过激活刺猬信号通路改善乙醇诱导的薄型子宫内膜并提高生育能力。