Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal?Fetal Interface of Non-Obese 1 Diabetic Mice and Improves Early Pregnancy Outcome

HAUK VANESSA; AZZAM SOFIA; CALO GUILLERMINA; GALLINO LUCILA; PAPARINI DANIEL; FRANCHI, ANA MARIA; RAMHORST, ROSANNA; PEREZ LEIROS, CLAUDIA

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2013 vol. 71 p. 120 - 130

1046-7408

ProblemImpaired pregnancy in non-obese diabetic (NOD) mice was related tolimited vascular remodeling and autoimmune background. Vasoactiveintestinal peptide (VIP) has anti-inflammatory and immunosuppressanteffects, so we explored its ability to modulate the immune microenvironmentat the early maternal?placental interface and improve pregnancyin NOD mice.Method of studyImplantation sites were isolated from pregnant NOD mice at gestationalday 9.5 and were incubated with VIP for evaluation of cytokine or transcriptionfactor expression by RT-PCR, immunoblotting, and immunohistochemistry.Alternatively, pregnant mice were injected with VIP atday 6.5 and studied at day 9.5.ResultsVIP and VPAC receptors were detected in viable implantation sites. VIPimmunostaining was found predominantly on trophoblast giant cells.The in vitro treatment of viable implantation sites with VIP increased IL-10, TGF-b, and Foxp3 expression. Sites with resorption processes presentedlower VIP expression, reduced suppressant markers, andincreased IL-17 and RORcT expression compared with viable sites andVIP reduced RORcT expression. Pregnant mice treated with VIP at day6.5 presented an even distribution of viable implantation sites with anincreased expression of IL-10, TGF- b, and Foxp3.ConclusionVIP induces an immunosuppressant profile at the early maternal?