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病例报告:羊膜微泡在慢性子宫内膜炎母马再生医学治疗中的应用

Case Report: Use of Amniotic Microvesicles for Regenerative Medicine Treatment of a Mare With Chronic Endometritis.

作者信息

Lange-Consiglio Anna, Funghi Federico, Cantile Carlo, Idda Antonella, Cremonesi Fausto, Riccaboni Pietro

机构信息

Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Via dell'Università, Lodi, Italy.

Independent Researcher, Grosseto, Italy.

出版信息

Front Vet Sci. 2020 Jun 17;7:347. doi: 10.3389/fvets.2020.00347. eCollection 2020.

Abstract

Chronic endometritis is an inflammation in the inner layer of uterine mucosa, with or without an infectious process, which affects the animal's fertility but not its general health. A variety of treatments has been adopted over the years but to date, no effective cures have been able to renew the injured tissue. Since the defects in the fetal-maternal communication are caused by degenerative changes due to chronic endometrial inflammation, our working hypothesis was a new approach to this disease by the regenerative medicine using amniotic derived microvesicles (MVs) for their anti-inflammatory and regenerative effects. The MVs are responsible for horizontal transfer of genetic materials, including microRNA (miRNAs) that are involved in paracrine communication between origin cells and target cells. Thus, intrauterine MV infusion may be beneficial in degenerative chronic endometritis and in the fetal-maternal talk. The selected mare was an 11-year-old Friesian, with a history of failed pregnancies despite numerous insemination attempts. Punctual and evident heats characterized the reproductive history, but no insemination attempts had been made for many years. The first (failed) insemination was when the mare was 9-years-old. In the next two reproductive seasons, other attempts were made at regular intervals but none was successful. After a final insemination attempt using a stallion of proven fertility, the collection of an 8-day old embryo suggested that the mare was affected by implantation failure related to endometritis. The mare was treated with two cycles of intrauterine administration of amniotic-derived MVs. The success of the intrauterine administration of MVs was demonstrated by an improvement in the classification of endometritis and in a successful artificial insemination (AI) with implantation of an embryo, as detected at day 14 and with a pregnancy that is still ongoing. Probably, MVs were able to restore the injured endometrium and re-establish the proper communication for a successful embryo implantation.

摘要

慢性子宫内膜炎是子宫黏膜内层的一种炎症,无论是否存在感染过程,它都会影响动物的生育能力,但不会影响其整体健康。多年来人们采用了多种治疗方法,但迄今为止,尚无有效的治愈方法能够修复受损组织。由于胎儿与母体之间的沟通缺陷是由慢性子宫内膜炎导致的退行性变化引起的,我们的工作假设是采用再生医学的新方法来治疗这种疾病,即使用羊膜来源的微泡(MVs),因其具有抗炎和再生作用。微泡负责遗传物质的水平转移,包括参与起源细胞与靶细胞之间旁分泌通讯的微小RNA(miRNAs)。因此,子宫内注入微泡可能对退行性慢性子宫内膜炎以及胎儿与母体的交流有益。所选的母马是一匹11岁的弗里斯兰马,尽管进行了多次授精尝试,但仍有多次妊娠失败的病史。其繁殖史的特点是发情准时且明显,但多年来未进行授精尝试。第一次(失败的)授精是在母马9岁时。在接下来的两个繁殖季节,定期进行了其他尝试,但均未成功。在使用一匹生育能力已得到证实的种马进行最后一次授精尝试后,收集到一个8天大的胚胎,这表明该母马受与子宫内膜炎相关的着床失败影响。对该母马进行了两个周期的子宫内羊膜来源微泡给药治疗。子宫内微泡给药的成功体现在子宫内膜炎分级得到改善,以及在第14天检测到成功的人工授精(AI)且胚胎着床,并且妊娠仍在继续。可能是微泡能够修复受损的子宫内膜,并重新建立成功胚胎着床所需的适当通讯。

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