Open AccessSynthetic PreImplantation Factor (sPIF) reduces inflammation and prevents preterm birth
Author(s) -
Marialuigia Spinelli,
Céline Boucard,
Fiorella Di Nicuolo,
Valérie Haesler,
Roberta Castellani,
Alfredo Pontecorvi,
Giovanni Scambia,
Chiara Granieri,
Eytan R. Barnea,
Daniel Surbek,
Martin Mueller,
Nicoletta Di Simone
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0232493
Subject(s) - inflammation , medicine , fetus , neuroprotection , immune system , pregnancy , immunology , biology , genetics
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.