Amniotic Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles for Equine Chronic Degenerative Endometritis Treatment.

Abstract

<h4>Background</h4>Equine chronic degenerative endometritis (CDE) is a progressive process characterized by endometrial fibrosis that could be responsible for alterations of uterine environment and foetal-maternal communication.<h4>Objectives</h4>The aim of this study was to try to restore this communication by intrauterine administrations of amniotic cell-derived extracellular vesicles (AMC-EVs) in a case series.<h4>Study design</h4>Twelve mares were selected on the basis of their reproductive history of early embryonic loss or abortion and clinical suspicion of CDE subsequently verified with histopathological examination of endometrial biopsies.<h4>Methods</h4>Gynaecological and ultrasound examinations and histopathological examination of endometrial biopsies were performed. Mares were divided into two groups: Seven mares in Group 1 received a single treatment cycle (corresponding to two intrauterine AMC-EV administrations), whereas five mares of Group 2 received two treatment cycles (corresponding to four intrauterine AMC-EV administrations). Each administration was of 20 billion AMC-EVs diluted in 50 mL of sterile saline solution.<h4>Results</h4>Eleven mares were able to establish pregnancy after the treatment with AMC-EVs without significant difference in pregnancy outcomes between one or two treatment cycles (six out of seven mares of Group 1 and all mares of Group 2 were pregnant), suggesting that one cycle may be sufficient. The histological condition of their endometrium did not show any improvement in Kenney-Doig classification, meaning AMC-EVs did not exert regenerative activity but probably contributed to re-establishing a functional paracrine interaction between embryo and maternal tissues.<h4>Main limitations</h4>This study has the limitation of the small number of animals enrolled and the lack of a control group. However, considering the large number of past artificial insemination attempts for each animal enrolled in this study, each mare could be considered self-control.<h4>Conclusions</h4>It would seem possible that AMC-EVs supported and enhanced foetal-maternal communication that was compromised by CDE.