title: PreImplantation Factor (PIF*) endogenously prevents preeclampsia: Promotes trophoblast invasion and reduces oxidative stress.
abstract: Preeclampsia is a unique pregnancy disorder whose patho-physiology is initiated early in gestation, while clinical manifestations typically occur in mid-to-late pregnancy. Thus, prevention should optimally be initiated in early gestation. The intimate interaction between PIF, secreted early by viable embryos, and its host-mother provides insight into putative mechanisms of preeclampsia prevention. PIF is instrumental at the two critical events underlying preeclampsia. At first, shallow implantation leads to impaired placentation, oxidative stress, protein misfolding, and endothelial dysfunction. Later in gestation, hyper-oxygenation due to overflow of maternally derived oxygenated blood compromises the placenta. The first is likely involved in early preeclampsia occurrence due to reduced effectiveness of trophoblast/uterus interaction. The latter is observed with later-onset preeclampsia, caused by a breakdown in placental blood flow regulation. We reported that 1. PIF promotes implantation, endometrium receptivity, trophoblast invasion and increases pro-tolerance trophoblastic HLA-G expression and, 2. PIF protects against oxidative stress and protein misfolding, interacting with specific targets in embryo, 3. PIF regulates systemic immunity to reduce oxidative stress. Using PIF as an early preventative preeclampsia intervention could ameliorate or even prevent the disease, whose current main solution is early delivery.
authors.affiliation: Society for the Investigation of Early Pregnancy, 1697 Lark Lane, Cherry Hill, NJ 08003, USA; BioIncept, LLC, 1697 Lark Lane, Cherry Hill, NJ 08003, USA. Electronic address: Barnea@earlypregnancy.org.
authors.forename: E R
authors.initials: ER
authors.lastname: Barnea
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France; Department of Biology of Reproduction, Cytogenetic, Gynecology and Obstetrics, Centre Hospitalier de Poissy-Saint Germain, 23 Boulevard Gambetta, Poissy, France. Electronic address: francois.vialard@uvsq.fr.
authors.forename: F
authors.initials: F
authors.lastname: Vialard
authors.affiliation: Department of Biology of Reproduction, Cytogenetic, Gynecology and Obstetrics, Centre Hospitalier de Poissy-Saint Germain, 23 Boulevard Gambetta, Poissy, France. Electronic address: hadia.moindjie@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Moindjie
authors.affiliation: Department of Obstetrics and Gynecology, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, Milano, Italy; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Women and Children's Center For Blood Disorders and Preeclampsia Advancement, Yale University School of Medicine, 333 Cedar Street, FMB 339B, New Haven, CT 06520-8063, USA. Electronic address: sara.ornaghi@yale.edu.
authors.forename: S
authors.initials: S
authors.lastname: Ornaghi
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France. Electronic address: marie-noelle.dieudonne@uvsq.fr.
authors.forename: M N
authors.initials: MN
authors.lastname: Dieudonne
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Women and Children's Center For Blood Disorders and Preeclampsia Advancement, Yale University School of Medicine, 333 Cedar Street, FMB 339B, New Haven, CT 06520-8063, USA. Electronic address: michael.paidas@yale.edu.
authors.forename: M J
authors.initials: MJ
authors.lastname: Paidas
mesh_terms: D010064:Embryo Implantation / Q000276:immunology*; D005260:Female; D006801:Humans; D018384:Oxidative Stress / Q000276:immunology*; D011225:Pre-Eclampsia / Q000276:immunology* / Q000517:prevention & control; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology*
chemical_list: D011257:Pregnancy Proteins; C000605122:preimplantation factor, human
keywords: Embryo protection; Oxidative stress; PreImplantation Factor (PIF); Preeclampsia prevention; Trophoblast invasion