Maternal Regulation of Embryonic Growth: The Role of Vasoactive Intestinal Peptide 1

ArticleinEndocrinology 140(2):917-24 · March 1999with11 Reads
DOI: 10.1210/en.140.2.917 · Source: PubMed
Abstract
Vasoactive intestinal peptide (VIP) is an important growth regulator of the embryonic day (E)9-E11 mouse. In comparably aged rat embryos, VIP messenger RNA (mRNA) is not detectable; however, peak concentrations of VIP in maternal rat serum indicate a nonembryonic source. In the current study, mouse maternal and embryonic tissues were examined from E6-E12. Although RT-PCR revealed VIP mRNA in E6-E7 conceptuses, by E8 (when extraembryonic tissues could be separated from the embryo), VIP mRNA was detected only in the decidua/trophoblast. Decidual/trophoblastic VIP mRNA decreased until E10, after which it was not detectable. VIP mRNA was not apparent in the embryo until E11-E12. At E9, VIP immunoreactivity was localized to abundant, diffuse cells in the decidua basalis, which were also immunoreactive for T cell markers. VIP binding sites were dense in the decidua/trophoblast at E6, but gradually decreased until E10, after which they were not apparent. VIP binding sites were detected in embryonic neuroepithelium by E9. The transient presence of VIP binding sites and mRNA in the decidua/trophoblast correlate with the critical period of VIP growth regulation, when VIP mRNA is absent in the embryo. These findings suggest that maternal lymphocytes are the source of VIP's regulating early postimplantation embryonic growth.
    • "Evidence of the VIP antiinflammatory and tolerogenic effects were provided by in vitro studies of human [20] and murine [21] cells and from studies in animal models of viral disease [22] and chronic inflammation23242526. In particular, during pregnancy, evidence from murine models and experimental designs with human leukocytes and trophoblast cells has indicated that trophoblast cells produce VIP and that it exerts immunomodulatory effects, promoting antiinflammatory and tolerogenic responses27282930. In experimental coculture designs with human cells, VIP modulated the immune–trophoblast cell interaction, inducing CD4 + CD25 + FoxP3 + cells, and reduced proinflammatory markers [31, 32] . "
    [Show abstract] [Hide abstract] ABSTRACT: Inducible regulatory T cells (Tregs) exert a timely and efficient immunosuppressive action at the critical peri-implantation stage essential for maternal tolerance to the conceptus. Vasoactive intestinal peptide (VIP) promotes anti-inflammatory and tolerogenic profiles through binding to VIP receptors on immune cells. We evaluated whether VIP produced by trophoblast cells induces Tregs during the early interaction of maternal leukocytes with trophoblast cells, thus contributing to maternal tolerance. We used an in vitro model of maternal leukocyte-trophoblast cell interaction represented by cocultures of fertile women's PBMCs with a human trophoblast cell line (Swan-71) and evaluated the effect of VIP added exogenously and of the endogenous polypeptide. VIP increased the frequency of CD4(+)CD25(+)FoxP3(+) cells after coculture, and these cells were able to suppress the maternal alloresponse. VIP also increased the frequency of CD4(+)IL10(+) and CD4(+)TGFβ(+) cells, but it did not modulate IFN-γ or IL-17 production. Swan-71 secreted VIP, and their coculture with maternal PBMCs significantly increased the frequency of Tregs. This effect was even more pronounced if the trophoblast cells had been pretreated with VIP. In both situations, the VIP antagonist prevented the increase in the frequency of CD4(+)Foxp3(+) cells, reflecting a specific effect of the polypeptide after the interaction with Swan-71 cells. Finally, the increase in CD4(+)CD25(+)FoxP3(+) frequency was prevented by an anti-TGF-β Ab and a VIP antagonist. These results suggest that VIP could have an active role in the immunoregulatory processes operating in the maternal-placental interface by contributing to the induction of Tregs through a mechanism involving TGF-β1. © Society for Leukocyte Biology.
    Full-text · Article · Apr 2015
    • "Endogenous actions of VIP were found in promoting hippocampal-dependent spatial discrimination in water maze learning (Glowa et al., 1992) and promoting embryonic brain development (Gressens et al., 1994; Spong et al., 1999; Zupan et al., 2000). The later does not relate directly to hippocampal function, is elicited by VIP originating in maternal placental lymphocytes (Gressens et al., 1994; Spong et al., 1999; Zupan et al., 2000) and is probably the cause for the cognitive impairment of the progeny of VIPdeficient female mice (Hill et al., 2007a; Stack et al., 2008). Thus, this study is of particular relevance to understand the role of endogenous VIP and hippocampal VPAC 1 receptors past the developmental stages, how they are endogenously activated and if they can constitute molecular targets to treat cognitive dysfunction. "
    [Show abstract] [Hide abstract] ABSTRACT: Vasoactive intestinal peptide (VIP), an important modulator of hippocampal synaptic transmission, influences exploration and hippocampal-dependent learning in rodents. Homosynaptic long-term depression (LTD) and depotentiation are two plasticity phenomena implicated in learning of behavior flexibility and spatial novelty detection. In this study, we investigated the influence of endogenous VIP on LTD and depotentiation induced by low-frequency stimulation (1 Hz, 900 pulses) of the hippocampal CA1 area in vitro in juvenile and young adult rats, respectively. LTD and depotentiation were enhanced by the VIP receptor antagonist Ac-Tyr(1) , D-Phe(2) GRF (1-29) and the selective VPAC1 receptor antagonist, PG 97-269, but not the selective VPAC2 receptor antagonist, PG 99-465. This action was mimicked by an anti-VIP antibody, suggesting that VIP, and not pituitary adenylate cyclase-activating polypeptide (PACAP), is the endogenous mediator of these effects. Selective inhibition of PAC1 receptors with PACAP (6-38) enhanced depotentiation, but not LTD. VPAC1 receptor blockade also revealed LTD in young adult rats, an effect abolished by the GABAA antagonist bicuculline, evidencing an involvement of GABAergic transmission. We conclude that inhibition of LTD and depotentiation by endogenous VIP occurs through VPAC1 receptor-mediated mechanisms and suggests that disinhibition of pyramidal cell dendrites is the most likely physiological mechanism underlying this effect. As such, VPAC1 receptor ligands may be considered promising pharmacological targets for treatment of cognitive dysfunction in diseases involving altered GABAergic circuits and pathological saturation of LTP/LTD like Down's syndrome and temporal lobe epilepsy. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Nov 2014
    • "We observed that trophoblast cells not only contributed to their differentiation in a TGFb-dependent pathway, but also secreted chemokines, such as RANTES, MCP1 (CCL2) and IL8, which were capable of selectively recruiting them (Ramhorst et al. 2012). Vasoactive intestinal peptide (VIP) is a pleiotropic peptide with embryotrophic, smooth-muscle-relaxing, prosecretory and immunomodulatory effects (Ekström et al. 1983, Spong et al. 1999, Gonzalez-Rey et al. 2007, Leceta et al. 2007, Couvineau & Laburthe 2012). VIP was shown to downregulate inflammatory factors and inhibit antigen-specific Th1-driven immune responses switching to a tolerogenic profile with the generation or expansion of Treg cells (Gonzalez-Rey et al. 2007, Leceta et al. 2007). "
    [Show abstract] [Hide abstract] ABSTRACT: During early pregnancy, the human uterus undergoes profound tissue remodeling characterized by leukocyte invasion and production of proinflammatory cytokines, followed by tissue repair and tolerance maintenance induction. Vasoactive intestinal peptide (VIP) is produced by trophoblast cells and modulates the maternal immune response towards a tolerogenic profile. Here, we evaluated the VIP/VPAC system contribution to endometrial renewal, inducing decidualization and the recruitment of induced regulatory T cells (iTregs) that accompany the implantation period. For that purpose, we used an in vitro model of decidualization with a human endometrial stromal cell line (HESC) stimulated with progesterone and LPS (Lipopolysaccharide) simulating the inflammatory response during implantation and human iTregs (CD4+CD25+FOXP3+) cells differentiated from naïve T cells obtained from fertile women peripheral blood monuclear cells. We observed that VIP and its receptor VPAC1 are constitutively expressed in HESC cells and progesterone increased VIP expression. Moreover, VIP induced RANTES expression by HESC, one of the main chemokines involved in T cell-recruitment and this effect is enhanced by the presence of progesterone and LPS. Finally, migration assays of iTregs toward conditioned media from HESC cells revealed that endogenous VIP production induced by P4 and LPS and RANTES production were involved since the anti-RANTES neutralizing Ab or VIP antagonist prevented their migration. We conclude that VIP may have an active role in the decidualization process thus contributing to iTregs recruitment toward endometrial stromal cells by increasing RANTES expression in a progesterone-dependent manner.
    Full-text · Article · Feb 2014
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