VIP induces an immunosuppressant microenvironment in the maternal-fetal interface of non obese diabetic (NOD) mice and improves pregnancy outcome

HAUK V; AZZAM S; GRASSO E; GALLINO L; CALO G; FRANCHI A; RAMHORST R; PÉREZ LEIRÓS C

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY

Wiley-Blackwell

Lugar: Copenhagen ; Año: 2014 vol. 71 p. 120 - 130

8755-8920

The loss of immune homeostasis at the maternal-placental interface in non obese diabetic (NOD) mice was related to inflammatory autoimmune prone background along with a defective activity of vasoactive mediators. Since vasoactive intestinal peptide (VIP) acts on immune and uterine tissues with anti-inflammatory, tolerogenic and smooth muscle relaxing effects, we explored its ability to promote an immunosuppressant microenvironment and improve pregnancy outcome in NOD mice. VIP and VPAC2 receptor expression was detected in pregnant uterus and deciduas but not in non-pregnant uterus. VIP treatment of implantation site explants increased VPAC2, TGFbeta, Foxp3 and IL-10 expression, similarly to progesterone treatment. VIP inhibited prostaglandin synthesis indicating functional receptors. Sites with resorption processes presented lower VIP and suppressant mediator expression than viable sites, whereas there was an increased COX-2 activity, IL-17 and RORgT expression. Pregnant NOD mice treated with VIP at gestational day 6 presented an even distribution of embryos along the horns with increased local expression of IL-10, TGF- β and Foxp3. We conclude that VIP treatment modulates inflammatory signals at the early maternal-fetal interface of prediabetic NOD mice and partially improves pregnancy outcome.