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. 1999 Feb;194(Pt 2):197–205. doi: 10.1046/j.1469-7580.1999.19420197.x

The effects of lithium on vascular development in the chick area vasculosa

JAMES J GILES 1,✉, JOHN G BANNIGAN 1
PMCID: PMC1467913  PMID: 10337951

Abstract

The effects of lithium on vascular development were examined using the chick embryo area vasculosa in shell-less culture as an experimental model. Embryos were explanted after 48 h in ovo and LiCl (50, 100, 150 and 200 μg in 10 μl water) was applied to the centre of the blastodisc. Controls were untreated or given equimolar amounts of NaCl. At 24 h and 48 h after treatment, untreated and NaCl controls were identical, having well developed extraembryonic vessels. At doses of 100 μg and greater, LiCl significantly inhibited normal vascular development and expansion of the area vasculosa in the majority of explants. In many specimens blood islands continued to form but their assembly into primitive vessels was prevented, indicating that lithium affects the mechanism regulating the assembly of vascular endothelium. At the same time the embryos were alive but retarded in development compared with controls. When LiCl (150 μg) was applied to cultures explanted after 72 h in ovo (when the primary vascular network had already formed through vasculogenesis) no adverse effects were seen. This suggests that lithium affects vasculogenesis but not angiogenesis. Treatment with myo-inositol completely reversed the effects of lithium in a time dependent manner indicating that the phosphatidylinositol second messenger cycle may be involved in the cellular events of vasculogenesis. Finally the results of this study show that the yolk sac vasculature is particularly vulnerable to lithium and the consequent effects of this interference on embryonic development are discussed.

Keywords: Vasculogenesis, angiogenesis, phosphatidylinositol cycle, myo-inositol

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Selected References

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  1. Allen W. E., Wilson D. J. Early embryonic angiogenesis in the chick area vasculosa. J Anat. 1993 Dec;183(Pt 3):579–585. [PMC free article] [PubMed] [Google Scholar]
  2. Baker L., Piddington R., Goldman A., Egler J., Moehring J. Myo-inositol and prostaglandins reverse the glucose inhibition of neural tube fusion in cultured mouse embryos. Diabetologia. 1990 Oct;33(10):593–596. doi: 10.1007/BF00400202. [DOI] [PubMed] [Google Scholar]
  3. Becchetti A., Whitaker M. Lithium blocks cell cycle transitions in the first cell cycles of sea urchin embryos, an effect rescued by myo-inositol. Development. 1997 Mar;124(6):1099–1107. doi: 10.1242/dev.124.6.1099. [DOI] [PubMed] [Google Scholar]
  4. Beck L., Jr, D'Amore P. A. Vascular development: cellular and molecular regulation. FASEB J. 1997 Apr;11(5):365–373. [PubMed] [Google Scholar]
  5. Berridge M. J., Downes C. P., Hanley M. R. Neural and developmental actions of lithium: a unifying hypothesis. Cell. 1989 Nov 3;59(3):411–419. doi: 10.1016/0092-8674(89)90026-3. [DOI] [PubMed] [Google Scholar]
  6. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Busa W. B., Gimlich R. L. Lithium-induced teratogenesis in frog embryos prevented by a polyphosphoinositide cycle intermediate or a diacylglycerol analog. Dev Biol. 1989 Apr;132(2):315–324. doi: 10.1016/0012-1606(89)90228-5. [DOI] [PubMed] [Google Scholar]
  8. Cohen L. S., Friedman J. M., Jefferson J. W., Johnson E. M., Weiner M. L. A reevaluation of risk of in utero exposure to lithium. JAMA. 1994 Jan 12;271(2):146–150. [PubMed] [Google Scholar]
  9. Dugan J. D., Jr, Lawton M. T., Glaser B., Brem H. A new technique for explantation and in vitro cultivation of chicken embryos. Anat Rec. 1991 Jan;229(1):125–128. doi: 10.1002/ar.1092290114. [DOI] [PubMed] [Google Scholar]
  10. Flamme I., Baranowski A., Risau W. A new model of vasculogenesis and angiogenesis in vitro as compared with vascular growth in the avian area vasculosa. Anat Rec. 1993 Sep;237(1):49–57. doi: 10.1002/ar.1092370106. [DOI] [PubMed] [Google Scholar]
  11. Flamme I., Risau W. Induction of vasculogenesis and hematopoiesis in vitro. Development. 1992 Oct;116(2):435–439. doi: 10.1242/dev.116.2.435. [DOI] [PubMed] [Google Scholar]
  12. Fong G. H., Rossant J., Gertsenstein M., Breitman M. L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 1995 Jul 6;376(6535):66–70. doi: 10.1038/376066a0. [DOI] [PubMed] [Google Scholar]
  13. Giles J. J., Bannigan J. G. The effects of lithium on neurulation stage mouse embryos. Arch Toxicol. 1997;71(8):519–528. doi: 10.1007/s002040050422. [DOI] [PubMed] [Google Scholar]
  14. Giles J. J., Kavanagh H. J., Bannigan J. G. A non-invasive photographic modification for recording early vascular development in the chick. J Microsc. 1995 Sep;179(Pt 3):282–285. doi: 10.1111/j.1365-2818.1995.tb03643.x. [DOI] [PubMed] [Google Scholar]
  15. Jurand A. Teratogenic activity of lithium carbonate: an experimental update. Teratology. 1988 Aug;38(2):101–111. doi: 10.1002/tera.1420380202. [DOI] [PubMed] [Google Scholar]
  16. Klug S., Collins M., Nagao T., Merker H. J., Neubert D. Effect of lithium on rat embryos in culture: growth, development, compartmental distribution and lack of a protective effect of inositol. Arch Toxicol. 1992;66(10):719–728. doi: 10.1007/BF01972623. [DOI] [PubMed] [Google Scholar]
  17. Marathe M. R., Thomas G. P. Embryotoxicity and teratogenicity of lithium carbonate in Wistar rat. Toxicol Lett. 1986 Nov;34(1):115–120. doi: 10.1016/0378-4274(86)90153-0. [DOI] [PubMed] [Google Scholar]
  18. Moore J. A. An assessment of lithium using the IEHR Evaluative Process for Assessing Human Developmental and Reproductive Toxicity of Agents. IEHR Expert Scientific Committee. Reprod Toxicol. 1995 Mar-Apr;9(2):175–210. doi: 10.1016/0890-6238(94)00069-7. [DOI] [PubMed] [Google Scholar]
  19. Nilsen N. O. Vascular abnormalities due to hyperthermia in chick embryos. Teratology. 1984 Oct;30(2):237–251. doi: 10.1002/tera.1420300211. [DOI] [PubMed] [Google Scholar]
  20. Noden D. M. Embryonic origins and assembly of blood vessels. Am Rev Respir Dis. 1989 Oct;140(4):1097–1103. doi: 10.1164/ajrccm/140.4.1097. [DOI] [PubMed] [Google Scholar]
  21. Pinter E., Reece E. A., Leranth C. Z., Garcia-Segura M., Hobbins J. C., Mahoney M. J., Naftolin F. Arachidonic acid prevents hyperglycemia-associated yolk sac damage and embryopathy. Am J Obstet Gynecol. 1986 Oct;155(4):691–702. doi: 10.1016/s0002-9378(86)80001-1. [DOI] [PubMed] [Google Scholar]
  22. Poole T. J., Coffin J. D. Vasculogenesis and angiogenesis: two distinct morphogenetic mechanisms establish embryonic vascular pattern. J Exp Zool. 1989 Aug;251(2):224–231. doi: 10.1002/jez.1402510210. [DOI] [PubMed] [Google Scholar]
  23. Price L. H., Heninger G. R. Lithium in the treatment of mood disorders. N Engl J Med. 1994 Sep 1;331(9):591–598. doi: 10.1056/NEJM199409013310907. [DOI] [PubMed] [Google Scholar]
  24. Risau W. Mechanisms of angiogenesis. Nature. 1997 Apr 17;386(6626):671–674. doi: 10.1038/386671a0. [DOI] [PubMed] [Google Scholar]
  25. Stewart R., Nelson J., Wilson D. J. Epidermal growth factor promotes chick embryonic angiogenesis. Cell Biol Int Rep. 1989 Nov;13(11):957–965. doi: 10.1016/0309-1651(89)90079-9. [DOI] [PubMed] [Google Scholar]
  26. Stewart R., Nelson J., Wilson D. J. Growth of the chick area vasculosa in ovo and in shell-less culture. J Anat. 1990 Oct;172:81–87. [PMC free article] [PubMed] [Google Scholar]
  27. Szabo K. T. Teratogenic effect of lithium carbonate in the foetal mouse. Nature. 1970 Jan 3;225(5227):73–75. doi: 10.1038/225073a0. [DOI] [PubMed] [Google Scholar]
  28. Warkany J. Teratogen update: lithium. Teratology. 1988 Dec;38(6):593–597. doi: 10.1002/tera.1420380607. [DOI] [PubMed] [Google Scholar]
  29. Wright P. S., Cross-Doersen D., Miller J. A., Jones W. D., Bitonti A. J. Inhibition of angiogenesis in vitro and in ovo with an inhibitor of cellular protein kinases, MDL 27032. J Cell Physiol. 1992 Sep;152(3):448–457. doi: 10.1002/jcp.1041520303. [DOI] [PubMed] [Google Scholar]

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