title: VIP treatment prevents embryo resorption by modulating efferocytosis and activation profile of maternal macrophages in the CBAxDBA resorption prone model.
abstract: Successful embryo implantation occurs followed by a local pro-inflammatory response subsequently shifted toward a tolerogenic one. VIP (vasoactive intestinal peptide) has embryotrofic, anti-inflammatory and tolerogenic effects. In this sense, we investigated whether the in vivo treatment with VIP contributes to an immunosuppressant local microenvironment associated with an improved pregnancy outcome in the CBA/J × DBA/2 resorption prone model. Pregnancy induced the expression of VIP, VPAC1 and VPAC2 in the uterus from CBA/J × DBA/2 mating females on day 8.5 of gestation compared with non-pregnant mice. VIP treatment (2 nmol/mouse i.p.) on day 6.5 significantly increased the number of viable implantation sites and improved the asymmetric distribution of implanted embryos. This effect was accompanied by a decrease in RORγt and an increase in TGF-β and PPARγ expression at the implantation sites. Moreover, VIP modulated the maternal peritoneal macrophages efferocytosis ability, tested using latex beads-FITC or apoptotic thymocytes, displaying an increased frequency of IL-10-producer F4/80 cells while did not modulate TNF-α and IL-12 secretion. The present data suggest that VIP treatment increases the number of viable embryos associated with an increase in the efferocytic ability of maternal macrophages which is related to an immunosuppressant microenvironment.
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires. IQUIBICEN-CONICET.
authors.forename: Lucila
authors.initials: L
authors.lastname: Gallino
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires. IQUIBICEN-CONICET.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Calo
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires. IQUIBICEN-CONICET.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Hauk
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires. IQUIBICEN-CONICET.
authors.forename: Laura
authors.initials: L
authors.lastname: Fraccaroli
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires. IQUIBICEN-CONICET.
authors.forename: Esteban
authors.initials: E
authors.lastname: Grasso
authors.affiliation: Institute of Experimental Medicine IMEX-CONICET, National Academy of Sciences, Buenos Aires.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vermeulen
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires. IQUIBICEN-CONICET.
authors.forename: Claudia Pérez
authors.initials: CP
authors.lastname: Leirós
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires. IQUIBICEN-CONICET.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ramhorst
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology; D005260:Female; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide