Spinelli, Marialuigia; Boucard, Céline; Di Nicuolo, Fiorella; Haesler, Valérie; Castellani, Roberta; Pontecorvi, Alfredo; Scambia, Giovanni; Granieri, Chiara; Barnea, Eytan R; Surbek, Daniel; Mueller, Martin; Di Simone, Nicoletta (2020). Synthetic PreImplantation Factor (sPIF) reduces inflammation and prevents preterm birth. PLoS ONE, 15(6), e0232493. Public Library of Science 10.1371/journal.pone.0232493
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Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality and spontaneous PTB is a major contributor. The preceding inflammation/infection contributes not only to spontaneous PTB but is associated with neonatal morbidities including impaired brain development. Therefore, control of exaggerated immune response during pregnancy is an attractive strategy. A potential candidate is synthetic PreImplantation Factor (sPIF) as sPIF prevents inflammatory induced fetal loss and has neuroprotective properties. Here, we tested maternal sPIF prophylaxis in pregnant mice subjected to a lipopolysaccharides (LPS) insult, which results in PTB. Additionally, we evaluated sPIF effects in placental and microglial cell lines. Maternal sPIF application reduced the LPS induced PTB rate significantly. Consequently, sPIF reduced microglial activation (Iba-1 positive cells) and preserved neuronal migration (Cux-2 positive cells) in fetal brains. In fetal brain lysates sPIF decreased IL-6 and INFγ concentrations. In-vitro, sPIF reduced Iba1 and TNFα expression in microglial cells and reduced the expression of pro-apoptotic (Bad and Bax) and inflammatory (IL-6 and NLRP4) genes in placental cell lines. Together, maternal sPIF prophylaxis prevents PTB in part by controlling exaggerated immune response. Given the sPIF`FDA Fast Track approval in non-pregnant subjects, we envision sPIF therapy in pregnancy.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pränatale Medizin |
UniBE Contributor: |
Spinelli, Marialuigia, Boucard, Céline, Haesler, Valérie, Surbek, Daniel, Müller, Martin (A) |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1932-6203 |
Publisher: |
Public Library of Science |
Language: |
English |
Submitter: |
Monika Zehr |
Date Deposited: |
12 Jan 2021 17:28 |
Last Modified: |
22 May 2023 09:44 |
Publisher DOI: |
10.1371/journal.pone.0232493 |
PubMed ID: |
32511256 |
BORIS DOI: |
10.48350/150116 |
URI: |
https://boris.unibe.ch/id/eprint/150116 |
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