D-手性肌醇在小鼠模型中可有效对抗子宫内膜异位症。

D-chiro-inositol effectively counteracts endometriosis in a mouse model.

作者信息

Placidi Martina, Casoli Giovanni, Vergara Teresa, Bianchi Andrea, Cocciolone Domenica, Zaccardi Silvia, Macchiarelli Guido, Palmerini Maria Grazia, Tatone Carla, Bevilacqua Arturo, Di Emidio Giovanna

机构信息

Department of Life, Health and Environmental Sciences, University of L'Aquila, Via G. Petrini, 67100, L'Aquila, Italy.

Department of Dynamic, Clinical Psychology and Health Studies, Sapienza University of Rome, 00185, Rome, Italy.

出版信息

Mol Med. 2025 Apr 11;31(1):134. doi: 10.1186/s10020-025-01178-6.

DOI:10.1186/s10020-025-01178-6

PMID:40211112

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11987403/

Abstract

BACKGROUND

Endometriosis, a common condition affecting 5-10% of women of reproductive age, is the growth of endometrial-like tissue outside the uterus, leading to pain and infertility. Current treatments, such as surgery and hormonal therapy, offer limited long-term benefits. This study investigated the potential of D-chiro inositol (DCI), a natural compound that influences ovarian steroidogenesis, to treat endometriosis and compared its efficacy with a progestin drug such as Dienogest (DG).

METHODS

We established a non-surgical mouse model of endometriosis in CD1 mice. Uterine horns were removed from donor mice, cut into fragments and inoculated in recipient mice by intraperitoneal injection. Endometriosis progression was assessed at 15, 21 and 28 days after transplantation, with the 28-day window being the most effective. The mice were then randomly assigned to four experimental groups, which received for 28 days: water (EMS); DCI 0.4 mg/die (DCI); DCI 0.2 mg/die and Dienogest 0.33 ng/die (DCI + DG); DG 0.67 ng/die (DG). At the end of the treatments, endometriotic lesions, ovaries and circulating estradiol levels were analyzed.

RESULTS

The results showed that treatment with DCI, both alone and in combination with DG, significantly reduced the number, size and vascularization of endometriotic lesions compared to the EMS control group. Histological analysis confirmed a decrease in endometriotic foci across all treatment groups, with the most pronounced effects in the DCI group. To investigate the underlying molecular mechanisms, we found that DCI led to a significant reduction in the expression of Sirt1 and an increase in E-Cadherin, indicating a reduction in EMT transition relevant for lesion development. In addition, DCI decreased cell proliferation and,blood vessel formation, as evaluated by PCNA and CD34, respectively. Futhermore, in the ovary, DCI treatment downregulated the expression of aromatase (Cyp19a1), the enzyme critical for estrogen biosynthesis, and increased the number of primordial to antral follicles, suggesting a beneficial effect on ovarian folliculogenesis.

CONCLUSIONS

By modulating proliferation, EMT transition and aromatase activity, DCI emerges as a promising compound for endometriosis treatment.

摘要

背景

子宫内膜异位症是一种常见疾病，影响5%-10%的育龄女性，是子宫外类似子宫内膜组织的生长，导致疼痛和不孕。目前的治疗方法，如手术和激素疗法，长期益处有限。本研究调查了D-手性肌醇（DCI）（一种影响卵巢类固醇生成的天然化合物）治疗子宫内膜异位症的潜力，并将其疗效与炔诺酮（DG）等孕激素药物进行比较。

方法

我们在CD1小鼠中建立了非手术性子宫内膜异位症小鼠模型。从供体小鼠身上取出子宫角，切成碎片，通过腹腔注射接种到受体小鼠体内。在移植后15、21和28天评估子宫内膜异位症的进展，28天的观察期最为有效。然后将小鼠随机分为四个实验组，连续28天接受以下处理：水（EMS）；DCI 0.4mg/只（DCI）；DCI 0.2mg/只和炔诺酮0.33ng/只（DCI+DG）；炔诺酮0.67ng/只（DG）。在治疗结束时，分析子宫内膜异位症病灶、卵巢和循环雌二醇水平。

结果

结果表明，与EMS对照组相比，单独使用DCI以及DCI与DG联合使用均显著减少了子宫内膜异位症病灶的数量、大小和血管生成。组织学分析证实所有治疗组的子宫内膜异位病灶均减少，其中DCI组效果最为显著。为了研究潜在的分子机制，我们发现DCI导致Sirt1表达显著降低，E-钙黏蛋白增加，表明与病灶发展相关的上皮-间质转化减少。此外，分别通过PCNA和CD34评估，DCI降低了细胞增殖和血管生成。此外，在卵巢中，DCI处理下调了芳香化酶（Cyp19a1）的表达，芳香化酶是雌激素生物合成的关键酶，并增加了原始卵泡到窦卵泡的数量，表明对卵巢卵泡发生有有益作用。