Vasoactive intestinal peptide (VIP) regulates growth in the early post-implantation embryo. Previous work has demonstrated that
peptide agonists (
SALLRSIPA and NAPVSIPQ) from downstream mediators that are regulated by VIP were able to prevent the alcohol-induced
fetal death, growth restriction and
microcephaly associated with
fetal alcohol syndrome. Here we evaluated the role of VIP in this mouse model of
fetal alcohol syndrome, to determine if fetal or maternal levels of VIP are altered. In addition, we evaluated whether
peptide treatment would alter the effects of alcohol on VIP levels. Treatment groups included control, alcohol, and alcohol+peptides. VIP levels were measured with
enzyme immunoassay [EIA] (Peninsula Laboratories, Belmont, CA). Quantitation of VIP expression was measured with rt-PCR using mimic
cDNA primers. Embryo/decidual VIP levels were similar in control and alcohol-treated groups 6 h
after treatment. However, in the embryo/deciduas at 12 and 24 h, VIP levels were below the EIA's detection limit in the alcohol-treated groups, and significantly lower than the control or
peptide-pretreated groups (p<0.05). Maternal cortex VIP levels were undetectable and significantly lower in the alcohol-treated group than control or peptide+alcohol group at 6 and 12 h (p<0.001). VIP
mRNA expression was quantitated in the embryo and deciduas, with a significant decline noted at 6 h to 58% of control levels (p=0.02). Pretreatment with the
peptides attenuated the alcohol-induced decrease in VIP
mRNA. These studies demonstrate that treatment with alcohol can decrease the expression and immunoreactivity of VIP in both maternal and fetal tissues. This alcohol-induced loss of a recognized regulator of embryonic growth and differentiation may contribute to the sequelae of toxicity observed in
fetal alcohol syndrome.