Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis

Lacombe, Arnaud; Lelièvre, Vincent; Roselli, Charles E.; Muller, Jean-Marc; Waschek, James A.; Vilain, Éric

doi:10.1677/joe-07-0102

Cited by 32 publications

(23 citation statements)

References 23 publications

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“…No differences were found between the two genotype (Figure 8; t =−0.60, p=0.55). However, both null and wild-type mice had high variation in blood testosterone levels, this variation was reported previously in other strains of mice [37–39]. Since hemolysis, the breakdown of erythrocytes with subsequent release of their intracellular contents, might interfere with the test results [40], we repeated the experiment using the BD Vacutainer® SST™ serum separation tubes.…”

Section: Resultsmentioning

confidence: 75%

Ephrin-A5 regulates inter-male aggression in mice

Sheleg

Yochum

Richardson

et al. 2015

Behavioural Brain Research

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The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5−/−) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5−/− mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5−/− mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice.

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Section: Resultsmentioning

confidence: 75%

Ephrin-A5 regulates inter-male aggression in mice

Sheleg

Yochum

Richardson

et al. 2015

Behavioural Brain Research

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“…For example, we have shown that targeted mutation of the VIP gene leads to several behavioral and endocrine dysfunctions (17)(18)(19)(20)(21). These mice show inflammation in the lung in basal conditions and airway hyperresponsiveness to methacholine aerosols (20,21), as well as pulmonary artery hypertension, right ventricular hypertrophy, and thickening of the walls of the pulmonary artery and branches (22).…”

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confidence: 99%

Vasoactive intestinal peptide loss leads to impaired CNS parenchymal T-cell infiltration and resistance to experimental autoimmune encephalomyelitis

Abad

Tan

Lopez

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The neuropeptide vasoactive intestinal peptide (VIP) has been shown to inhibit macrophage proinflammatory actions, promote a positive Th2/Th1 balance, and stimulate regulatory T-cell production. The fact that this peptide is highly efficacious in animal models of inflammatory diseases such as collagen-induced arthritis and experimental autoimmune encephalomyelitis (EAE) suggests that the endogenous peptide might normally provide protection against such pathologies. We thus studied the response of VIP-deficient (i.e., VIP KO) mice to myelin oligodendrocyte protein-induced EAE. Surprisingly, VIP KO mice were almost completely resistant to EAE, with delayed onset and mild or absent clinical profile. Despite this, flow cytometric analyses and antigen-rechallenge experiments indicated that myelin oligodendrocyte protein-treated VIP KO mice exhibited robust Th1/ Th17 cell inductions and antigen-specific proliferation and cytokine responses. Moreover, adoptive transfer of lymphocytes from immunized VIP KO mice to WT recipients resulted in full-blown EAE, supporting their encephalitogenic potential. In contrast, transfer of encephalitogenic WT cells to VIP KO hosts did not produce EAE, suggesting that loss of VIP specifically affected the effector phase of the disease. Histological analyses indicated that CD4 T cells entered the meningeal and perivascular areas of VIP-deficient mice, but that parenchymal infiltration was strongly impaired. Finally, VIP pretreatment of VIP KO mice before immunization was able to restore their sensitivity to EAE. These results indicate that VIP plays an unanticipated permissive and/or proinflammatory role in the propagation of the inflammatory response in the CNS, a finding with potential therapeutic relevance in autoimmune neuroinflammatory diseases such as multiple sclerosis.neuropeptide | multiple sclerosis | inflammation T he 28-aa neuropeptide vasoactive intestinal peptide (VIP) was initially discovered in the lung and intestine, where it exhibits potent vasodilator activity (1). It belongs to the secretin family and has high homology to pituitary adenylyl cyclase-activating polypeptide, with which it shares its two high-affinity G proteincoupled receptors (VPAC1 and VPAC2) (2). Widely distributed in neurons in the CNS and periphery, VIP is also present in lymphocytes and innervation within lymphoid organs (3-5). In the immune system, VIP has multiple and complex actions on myeloid and lymphoid cells (6, 7). The fact that VIP inhibits the release of proinflammatory mediators by activated macrophages, promotes Th2 versus Th1 responses, and induces the generation of regulatory T cells (Tregs), suggested that its receptors may be targets for anti-inflammatory drugs. Accordingly, subsequent studies showed that VIP treatment inhibits ongoing inflammatory responses in murine models of septic shock, Crohn's disease, and rheumatoid arthritis (8-11). However, the role of the endogenous peptide in maintaining the balance between potentially harmful and beneficial actions of the immune system r...

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“…Although the VIP−/− female mice also exhibit an advanced phase angle of entrainment, its magnitude is half that of their male counterparts (Table 2), suggesting there is a sex-dependent effect of the mutation. Additional sex-dependent effects include the reduced amount of activity specific to the VIP−/− males, which may be mediated by testosterone, also reduced in VIP−/− males (Lacombe et al, 2007). Physiologically, our data indicates that the VIP−/− females have severe deficits in the expression of daily rhythms in spontaneous electrical activity (Fig.…”

Section: Discussionmentioning

confidence: 99%

Disrupted Reproduction, Estrous Cycle, and Circadian Rhythms in Female Mice Deficient in Vasoactive Intestinal Peptide

et al. 2014

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The female reproductive cycle is gated by the circadian timing system and may be vulnerable to disruptions in the circadian system. Prior work suggests that vasoactive intestinal peptide (VIP) expressing neurons in the suprachiasmatic nucleus (SCN) are one pathway by which the circadian clock can influence the estrous cycle but the impact of the loss of this peptide on reproduction has not been assessed. In the present study, we first examine the impact of the genetic loss of the neuropeptide VIP on the reproductive success of female mice. Significantly, mutant females produced about half the offspring of their wild type sisters even when mated to the same males. We also find that VIP-deficient females exhibit a disrupted estrous cycle i.e. ovulation occurs less frequently and results in the release of fewer oocytes compared to controls. Circadian rhythms of wheel running activity are disrupted in the female mutant mice as are the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibit lower amplitude oscillations with altered phase relationships between the SCN and peripheral oscillators as measured by PER2-driven bioluminescence. The simplest explanation of our data is that the loss of VIP results in a weakened SCN oscillator which reduces the synchronization of the female circadian system. These results clarify one of the mechanisms by which disruption of the circadian system reduces female reproductive success.

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Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis

Cited by 32 publications

References 23 publications

Ephrin-A5 regulates inter-male aggression in mice

Ephrin-A5 regulates inter-male aggression in mice

Vasoactive intestinal peptide loss leads to impaired CNS parenchymal T-cell infiltration and resistance to experimental autoimmune encephalomyelitis

Disrupted Reproduction, Estrous Cycle, and Circadian Rhythms in Female Mice Deficient in Vasoactive Intestinal Peptide

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