Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Jan 1;97(1):202–208. doi: 10.1172/JCI118391

Maternal vasoactive intestinal peptide and the regulation of embryonic growth in the rodent.

J M Hill 1, S K McCune 1, R J Alvero 1, G W Glazner 1, K A Henins 1, S F Stanziale 1, J R Keimowitz 1, D E Brenneman 1
PMCID: PMC507080  PMID: 8550835

Abstract

Vasoactive intestinal peptide (VIP) has been shown to regulate early postimplantation growth in rodents through central nervous system receptors. However, the source of VIP mediating these effects is unknown. Although VIP binding sites are present prenatally, VIP mRNA was not detected in the rat central nervous system before birth and was detected in the periphery only during the last third of pregnancy. In the present study, the embryonic day (E11) rat embryo/trophoblast was shown to have four times the VIP concentration of the E17 fetus and to have VIP receptors in the central nervous system. However, no VIP mRNA was detected in the E11 rat embryo or embryonic membranes by in situ hybridization or reverse transcriptase-PCR. RIA of rat maternal serum revealed a peak in VIP concentration at days E10-E12 of pregnancy, with VIP rising to levels 6-10-fold higher than during the final third of pregnancy. After intravenous administration of radiolabeled VIP to pregnant female mice, undegraded VIP was found in the E10 embryo. These results suggest that maternal tissues may provide neuroendocrine support for embryonic growth through a surge of VIP during early postimplantation development in the rodent.

Full Text

The Full Text of this article is available as a PDF (358.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman J., Bayer S. A. The development of the rat spinal cord. Adv Anat Embryol Cell Biol. 1984;85:1–164. doi: 10.1007/978-3-642-69537-7. [DOI] [PubMed] [Google Scholar]
  2. Brenneman D. E., Eiden L. E., Siegel R. E. Neurotrophic action of VIP on spinal cord cultures. Peptides. 1985;6 (Suppl 2):35–39. doi: 10.1016/0196-9781(85)90132-9. [DOI] [PubMed] [Google Scholar]
  3. Brenneman D. E., Eiden L. E. Vasoactive intestinal peptide and electrical activity influence neuronal survival. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1159–1162. doi: 10.1073/pnas.83.4.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brenneman D. E., Hill J. M., Glazner G. W., Gozes I., Phillips T. W. Interleukin-1 alpha and vasoactive intestinal peptide: enigmatic regulation of neuronal survival. Int J Dev Neurosci. 1995 Jun-Jul;13(3-4):187–200. doi: 10.1016/0736-5748(95)00014-8. [DOI] [PubMed] [Google Scholar]
  5. Brenneman D. E., Neale E. A., Foster G. A., d'Autremont S. W., Westbrook G. L. Nonneuronal cells mediate neurotrophic action of vasoactive intestinal peptide. J Cell Biol. 1987 Jun;104(6):1603–1610. doi: 10.1083/jcb.104.6.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brenneman D. E., Nicol T., Warren D., Bowers L. M. Vasoactive intestinal peptide: a neurotrophic releasing agent and an astroglial mitogen. J Neurosci Res. 1990 Mar;25(3):386–394. doi: 10.1002/jnr.490250316. [DOI] [PubMed] [Google Scholar]
  7. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. Danielson P. E., Forss-Petter S., Brow M. A., Calavetta L., Douglass J., Milner R. J., Sutcliffe J. G. p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. DNA. 1988 May;7(4):261–267. doi: 10.1089/dna.1988.7.261. [DOI] [PubMed] [Google Scholar]
  9. Fatatis A., Holtzclaw L. A., Avidor R., Brenneman D. E., Russell J. T. Vasoactive intestinal peptide increases intracellular calcium in astroglia: synergism with alpha-adrenergic receptors. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2036–2040. doi: 10.1073/pnas.91.6.2036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Giladi E., Shani Y., Gozes I. The complete structure of the rat VIP gene. Brain Res Mol Brain Res. 1990 Apr;7(3):261–267. doi: 10.1016/0169-328x(90)90036-d. [DOI] [PubMed] [Google Scholar]
  11. Gozes I., McCune S. K., Jacobson L., Warren D., Moody T. W., Fridkin M., Brenneman D. E. An antagonist to vasoactive intestinal peptide affects cellular functions in the central nervous system. J Pharmacol Exp Ther. 1991 Jun;257(3):959–966. [PubMed] [Google Scholar]
  12. Gozes I., Schächter P., Shani Y., Giladi E. Vasoactive intestinal peptide gene expression from embryos to aging rats. Neuroendocrinology. 1988 Jan;47(1):27–31. doi: 10.1159/000124886. [DOI] [PubMed] [Google Scholar]
  13. Gressens P., Hill J. M., Gozes I., Fridkin M., Brenneman D. E. Growth factor function of vasoactive intestinal peptide in whole cultured mouse embryos. Nature. 1993 Mar 11;362(6416):155–158. doi: 10.1038/362155a0. [DOI] [PubMed] [Google Scholar]
  14. Gressens P., Hill J. M., Paindaveine B., Gozes I., Fridkin M., Brenneman D. E. Severe microcephaly induced by blockade of vasoactive intestinal peptide function in the primitive neuroepithelium of the mouse. J Clin Invest. 1994 Nov;94(5):2020–2027. doi: 10.1172/JCI117555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hill J. M., Agoston D. V., Gressens P., McCune S. K. Distribution of VIP mRNA and two distinct VIP binding sites in the developing rat brain: relation to ontogenic events. J Comp Neurol. 1994 Apr 8;342(2):186–205. doi: 10.1002/cne.903420204. [DOI] [PubMed] [Google Scholar]
  16. Hill J. M., Harris A., Hilton-Clarke D. I. Regional distribution of guanine nucleotide-sensitive and guanine nucleotide-insensitive vasoactive intestinal peptide receptors in rat brain. Neuroscience. 1992 Jun;48(4):925–932. doi: 10.1016/0306-4522(92)90280-f. [DOI] [PubMed] [Google Scholar]
  17. Léger J., Czernichow P. Retard de croissance intra-utérin. Pronostic statural et perspectives thérapeutiques. Presse Med. 1994 Jun 4;23(21):969–971. [PubMed] [Google Scholar]
  18. McCormick M. C. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med. 1985 Jan 10;312(2):82–90. doi: 10.1056/NEJM198501103120204. [DOI] [PubMed] [Google Scholar]
  19. Medlock E. S., Kaplan D. L., Cecchini M., Ulich T. R., del Castillo J., Andresen J. Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis. Blood. 1993 Feb 15;81(4):916–922. [PubMed] [Google Scholar]
  20. Moody T. W., Taylor D. P., Pert C. B. Effects of guanine nucleotides on CNS neuropeptide receptors. J Supramol Struct Cell Biochem. 1981;15(2):153–159. doi: 10.1002/jsscb.1981.380150206. [DOI] [PubMed] [Google Scholar]
  21. Morreale de Escobar G., Pastor R., Obregon M. J., Escobar del Rey F. Effects of maternal hypothyroidism on the weight and thyroid hormone content of rat embryonic tissues, before and after onset of fetal thyroid function. Endocrinology. 1985 Nov;117(5):1890–1900. doi: 10.1210/endo-117-5-1890. [DOI] [PubMed] [Google Scholar]
  22. Nishizawa M., Hayakawa Y., Yanaihara N., Okamoto H. Nucleotide sequence divergence and functional constraint in VIP precursor mRNA evolution between human and rat. FEBS Lett. 1985 Apr 8;183(1):55–59. doi: 10.1016/0014-5793(85)80953-4. [DOI] [PubMed] [Google Scholar]
  23. Obregon M. J., Mallol J., Pastor R., Morreale de Escobar G., Escobar del Rey F. L-thyroxine and 3,5,3'-triiodo-L-thyronine in rat embryos before onset of fetal thyroid function. Endocrinology. 1984 Jan;114(1):305–307. doi: 10.1210/endo-114-1-305. [DOI] [PubMed] [Google Scholar]
  24. Oláh Z., Lehel C., Anderson W. B., Brenneman D. E., van Agoston D. Subnanomolar concentration of VIP induces the nuclear translocation of protein kinase C in neonatal rat cortical astrocytes. J Neurosci Res. 1994 Nov 1;39(4):355–363. doi: 10.1002/jnr.490390402. [DOI] [PubMed] [Google Scholar]
  25. Ottesen B., Ulrichsen H., Fahrenkrug J., Larsen J. J., Wagner G., Schierup L., Søndergaard F. Vasoactive intestinal polypeptide and the female genital tract: relationship to reproductive phase and delivery. Am J Obstet Gynecol. 1982 Jun 15;143(4):414–420. doi: 10.1016/0002-9378(82)90083-7. [DOI] [PubMed] [Google Scholar]
  26. Peeters L. L. The effect of early maternal maladaptation on fetal growth. J Perinat Med. 1994;22 (Suppl 1):9–17. doi: 10.1515/jpme.1994.22.s1.9. [DOI] [PubMed] [Google Scholar]
  27. Pincus D. W., DiCicco-Bloom E. M., Black I. B. Vasoactive intestinal peptide regulates mitosis, differentiation and survival of cultured sympathetic neuroblasts. Nature. 1990 Feb 8;343(6258):564–567. doi: 10.1038/343564a0. [DOI] [PubMed] [Google Scholar]
  28. Pincus D. W., DiCicco-Bloom E. M., Black I. B. Vasoactive intestinal peptide regulation of neuroblast mitosis and survival: role of cAMP. Brain Res. 1990 Apr 30;514(2):355–357. doi: 10.1016/0006-8993(90)91433-h. [DOI] [PubMed] [Google Scholar]
  29. Robertson S. A., Seamark R. F. Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus. Reprod Fertil Dev. 1992;4(4):435–448. doi: 10.1071/rd9920435. [DOI] [PubMed] [Google Scholar]
  30. Tyrrell S., Landis S. C. The appearance of NPY and VIP in sympathetic neuroblasts and subsequent alterations in their expression. J Neurosci. 1994 Jul;14(7):4529–4547. doi: 10.1523/JNEUROSCI.14-07-04529.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Unterman T. G., Buchanan T. A., Freinkel N. Access of maternal insulin to the rat conceptus prior to allantoic placentation. Diabetes Res. 1989 Mar;10(3):115–120. [PubMed] [Google Scholar]
  32. Wegman M. E. Annual summary of vital statistics--1991. Pediatrics. 1992 Dec;90(6):835–845. [PubMed] [Google Scholar]
  33. Young W. S., 3rd, Mezey E., Siegel R. E. Vasopressin and oxytocin mRNAs in adrenalectomized and Brattleboro rats: analysis by quantitative in situ hybridization histochemistry. Brain Res. 1986 Dec;387(3):231–241. doi: 10.1016/0169-328x(86)90029-x. [DOI] [PubMed] [Google Scholar]
  34. Zolti M., Ben-Rafael Z., Meirom R., Shemesh M., Bider D., Mashiach S., Apte R. N. Cytokine involvement in oocytes and early embryos. Fertil Steril. 1991 Aug;56(2):265–272. doi: 10.1016/s0015-0282(16)54483-5. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES