title: Vasoactive intestinal peptide induces an immunosuppressant microenvironment in the maternal-fetal interface of non-obese diabetic mice and improves early pregnancy outcome.
abstract: OBJECTIVE
  Impaired pregnancy in non-obese diabetic (NOD) mice was related to limited vascular remodeling and autoimmune background. Vasoactive intestinal peptide (VIP) has anti-inflammatory and immunosuppressant effects, so we explored its ability to modulate the immune microenvironment at the early maternal-placental interface and improve pregnancy in NOD mice.
  
  
  METHODS
  Implantation sites were isolated from pregnant NOD mice at gestational day 9.5 and were incubated with VIP for evaluation of cytokine or transcription factor expression by RT-PCR, immunoblotting, and immunohistochemistry. Alternatively, pregnant mice were injected with VIP at day 6.5 and studied at day 9.5.
  
  
  RESULTS
  VIP and VPAC receptors were detected in viable implantation sites. VIP immunostaining was found predominantly on trophoblast giant cells. The in vitro treatment of viable implantation sites with VIP increased IL-10, TGF-β, and Foxp3 expression. Sites with resorption processes presented lower VIP expression, reduced suppressant markers, and increased IL-17 and RORγT expression compared with viable sites and VIP reduced RORγT expression. Pregnant mice treated with VIP at day 6.5 presented an even distribution of viable implantation sites with an increased expression of IL-10, TGF- β, and Foxp3.
  
  
  CONCLUSIONS
  VIP induces an immunosuppressant profile at the early maternal-placental interface of NOD mice and improves pregnancy outcome.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Hauk
authors.forename: Sofía
authors.initials: S
authors.lastname: Azzam
authors.forename: Guillermina
authors.initials: G
authors.lastname: Calo
authors.forename: Lucila
authors.initials: L
authors.lastname: Gallino
authors.forename: Daniel
authors.initials: D
authors.lastname: Paparini
authors.forename: Ana
authors.initials: A
authors.lastname: Franchi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ramhorst
authors.forename: Claudia
authors.initials: C
authors.lastname: Pérez Leirós
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007108:Immune Tolerance; D008431:Maternal-Fetal Exchange; D051379:Mice; D016688:Mice, Inbred NOD; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D011256:Pregnancy Outcome; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism; D014599:Uterus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide
keywords: Foxp3; IL-10; TGF-β; early pregnancy; non-obese diabetic mice; vasoactive intestinal peptide