Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal–Fetal Interface of Non-Obese Diabetic Mice and Improves Early Pregnancy Outcome
Article first published online: 28 OCT 2013
© 2013 John Wiley & Sons Ltd
American Journal of Reproductive Immunology
Volume 71, Issue 2, pages 120–130, February 2014
How to Cite
VIP induces an immunosuppressant microenvironment in the maternal–fetal interface of non-obese diabetic mice and improves early pregnancy outcome. Am J Reprod Immunol 2014; 71: 120–130, , , , , , , .
- Issue published online: 10 JAN 2014
- Article first published online: 28 OCT 2013
- Manuscript Accepted: 18 SEP 2013
- Manuscript Received: 3 JUL 2013
- National Agency of Sciences and Technology ANPCyT. Grant Number: PICT 2011-0144
- National Research Council CONICET. Grant Number: PIP 2012-2015
- University of Buenos Aires. Grant Numbers: UBACyT 20020100100505, UBACyT 20020090200034
- early pregnancy;
- non-obese diabetic mice;
- vasoactive intestinal peptide
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.
Method of study
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.
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.
VIP induces an immunosuppressant profile at the early maternal–placental interface of NOD mice and improves pregnancy outcome.