Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis

Persistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the o...

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Main Authors: Anna Lange-Consiglio, Giulia Gaspari, Federico Funghi, Emanuele Capra, Marina Cretich, Roberto Frigerio, Giampaolo Bosi, Fausto Cremonesi
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/6/5166
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author Anna Lange-Consiglio
Giulia Gaspari
Federico Funghi
Emanuele Capra
Marina Cretich
Roberto Frigerio
Giampaolo Bosi
Fausto Cremonesi
author_facet Anna Lange-Consiglio
Giulia Gaspari
Federico Funghi
Emanuele Capra
Marina Cretich
Roberto Frigerio
Giampaolo Bosi
Fausto Cremonesi
author_sort Anna Lange-Consiglio
collection DOAJ
description Persistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the onset of PPBIE was investigated. Stallion semen was supplemented with extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) at the time of insemination to prevent or limit the development of PPBIE. Before use in mares, a dose–response curve was produced to evaluate the effect of AMSC-EVs on spermatozoa, and an optimal concentration of 400 × 10<sup>6</sup> EVs with 10 × 10<sup>6</sup> spermatozoa/mL was identified. At this concentration, sperm mobility parameters were not negatively affected. Sixteen susceptible mares were enrolled and inseminated with semen (n = 8; control group) or with semen supplemented with EVs (n = 8; EV group). The supplementation of AMSC-EVs to semen resulted in a reduction in polymorphonuclear neutrophil (PMN) infiltration as well as intrauterine fluid accumulation (IUF; <i>p</i> < 0.05). There was a significant reduction in intrauterine cytokine levels (<i>p</i> < 0.05) for TNF-α and IL-6 and an increase in anti-inflammatory IL-10 in mares in the EV group, suggesting successful modulation of the post-insemination inflammatory response. This procedure may be useful for mares susceptible to PPBIE.
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spelling doaj.art-3574ae63248f4f94974296a2477087252023-11-17T11:30:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246516610.3390/ijms24065166Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced EndometritisAnna Lange-Consiglio0Giulia Gaspari1Federico Funghi2Emanuele Capra3Marina Cretich4Roberto Frigerio5Giampaolo Bosi6Fausto Cremonesi7Department of Veterinary Medicine and Animal Science (DIVAS), Università degli Studi di Milano, Via dell’Università, 6, 26900 Lodi, ItalyDepartment of Veterinary Medicine and Animal Science (DIVAS), Università degli Studi di Milano, Via dell’Università, 6, 26900 Lodi, ItalyIndependent Researcher, 58100 Grosseto, ItalyIstituto di Biologia e Biotecnologia Agraria (IBBA), Consiglio Nazionale delle Ricerche (CNR), 26900 Lodi, ItalyIstituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC), Consiglio Nazionale delle Ricerche (CNR), 20133 Milan, ItalyIstituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC), Consiglio Nazionale delle Ricerche (CNR), 20133 Milan, ItalyDepartment of Veterinary Medicine and Animal Science (DIVAS), Università degli Studi di Milano, Via dell’Università, 6, 26900 Lodi, ItalyDepartment of Veterinary Medicine and Animal Science (DIVAS), Università degli Studi di Milano, Via dell’Università, 6, 26900 Lodi, ItalyPersistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the onset of PPBIE was investigated. Stallion semen was supplemented with extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) at the time of insemination to prevent or limit the development of PPBIE. Before use in mares, a dose–response curve was produced to evaluate the effect of AMSC-EVs on spermatozoa, and an optimal concentration of 400 × 10<sup>6</sup> EVs with 10 × 10<sup>6</sup> spermatozoa/mL was identified. At this concentration, sperm mobility parameters were not negatively affected. Sixteen susceptible mares were enrolled and inseminated with semen (n = 8; control group) or with semen supplemented with EVs (n = 8; EV group). The supplementation of AMSC-EVs to semen resulted in a reduction in polymorphonuclear neutrophil (PMN) infiltration as well as intrauterine fluid accumulation (IUF; <i>p</i> < 0.05). There was a significant reduction in intrauterine cytokine levels (<i>p</i> < 0.05) for TNF-α and IL-6 and an increase in anti-inflammatory IL-10 in mares in the EV group, suggesting successful modulation of the post-insemination inflammatory response. This procedure may be useful for mares susceptible to PPBIE.https://www.mdpi.com/1422-0067/24/6/5166mareendometritisuterine fluid accumulationpolymorphonuclear neutrophil infiltrationregenerative medicine
spellingShingle Anna Lange-Consiglio
Giulia Gaspari
Federico Funghi
Emanuele Capra
Marina Cretich
Roberto Frigerio
Giampaolo Bosi
Fausto Cremonesi
Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis
International Journal of Molecular Sciences
mare
endometritis
uterine fluid accumulation
polymorphonuclear neutrophil infiltration
regenerative medicine
title Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis
title_full Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis
title_fullStr Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis
title_full_unstemmed Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis
title_short Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis
title_sort amniotic mesenchymal derived extracellular vesicles and their role in the prevention of persistent post breeding induced endometritis
topic mare
endometritis
uterine fluid accumulation
polymorphonuclear neutrophil infiltration
regenerative medicine
url https://www.mdpi.com/1422-0067/24/6/5166
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