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

Authors

  • Vanesa Hauk,

    1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
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  • Sofía Azzam,

    1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
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  • Guillermina Calo,

    1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
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  • Lucila Gallino,

    1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
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  • Daniel Paparini,

    1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
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  • Ana Franchi,

    1. Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Buenos Aires, Argentina
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  • Rosanna Ramhorst,

    1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
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  • Claudia Pérez Leirós

    Corresponding author
    1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
    • Correspondence

      Claudia Pérez Leirós, Ciudad Universitaria. Pab II. 4th floor.

      1428 Buenos Aires, Argentina.

      E-mail: cpleiros@qb.fcen.uba.ar

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Abstract

Problem

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.

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.

Conclusion

VIP induces an immunosuppressant profile at the early maternal–placental interface of NOD mice and improves pregnancy outcome.

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