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

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.

Extracellular vesicles in low volume uterine lavage and serum: novel and promising biomarker for endometritis in Arabian mares

“…Therefore, the exchange of EVs cargo between cells favors cell-cell communication and regulation of the immune response [ 15 ]. Inflammation of the inner layer of uterine tissues, either due to an infectious agents (bacteria& fungi) or non-infectious agents (trauma& sperm) is the main cause of sub-fertility in mares [ 24 , 38 ]. The successful resolution of inflammation is a critical step to maintain uterine homeostasis and subsequently provide the optimum milieu for the embryonic development [ 20 ].…”

The Biological Function of Extracellular Vesicles during Fertilization, Early Embryo—Maternal Crosstalk and Their Involvement in Reproduction: Review and Overview

“…In addition, their ability to promote re-epithelialization of skin wounds and stroke recovery has been reported [178]. Recently, amniotic derived EVs were used to treat endometritis in mare with the goal of achieving successful pregnancy [179]. This mare was an 11-year-old Friesian, with a history of failed pregnancies despite numerous insemination attempts for many years.…”

“…Extracellular vesicles can be administered via intravenous, subcutaneous, intraperitoneal, oral, and intranasal routes to reach the desired in vivo target sites, depending on the intended therapeutic action and tissues to be targeted [180]. In the paper by Lange-Consiglio et al [179] EVs were administered by the intravaginal rout. The biodistribution and targeting potential of EVs is dependent on EV sizes, surface markers, and their isolation methods.…”

Bone marrow‐derived mesenchymal stem cells microvesicles stabilize atherosclerotic plaques by inhibiting NLRP3‐mediated macrophage pyroptosis

“…As a mechanism of intercellular communication, MVs can transfer molecules such as DNA, mRNA, and miR from their origin cells to receptor cells (Lange‐Consiglio et al, 2020; G. Qiu et al, 2018). Ward et al (2018) have also shown that BMSCs‐MVs carry effective angiogenic cytokines and mRNA molecules to affect the local environment.…”