Full Text:   <1770>

CLC number: R78

On-line Access: 

Received: 2007-12-24

Revision Accepted: 2008-02-14

Crosschecked: 0000-00-00

Cited: 11

Clicked: 3734

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2008 Vol.9 No.4 P.306~312


A preliminary study on the teratogenesis of dexamethasone and the preventive effect of vitamin B12 on murine embryonic palatal shelf fusion in vitro

Author(s):  Sheng-jun LU, Wei HE, Bing SHI, Tian MENG, Xiao-yu LI, Yu-rong LIU

Affiliation(s):  State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu 610041, China; more

Corresponding email(s):   shibingcn@sina.com, tianmeng_scu@yahoo.com.cn

Key Words:  Dexamethasone, Vitamin B12, Organ culture, Cleft palate, Medial edge epithelial cells

Sheng-jun LU, Wei HE, Bing SHI, Tian MENG, Xiao-yu LI, Yu-rong LIU. A preliminary study on the teratogenesis of dexamethasone and the preventive effect of vitamin B12 on murine embryonic palatal shelf fusion in vitro[J]. Journal of Zhejiang University Science B, 2008, 9(4): 306~312.

@article{title="A preliminary study on the teratogenesis of dexamethasone and the preventive effect of vitamin B12 on murine embryonic palatal shelf fusion in vitro",
author="Sheng-jun LU, Wei HE, Bing SHI, Tian MENG, Xiao-yu LI, Yu-rong LIU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T A preliminary study on the teratogenesis of dexamethasone and the preventive effect of vitamin B12 on murine embryonic palatal shelf fusion in vitro
%A Sheng-jun LU
%A Wei HE
%A Bing SHI
%A Tian MENG
%A Xiao-yu LI
%A Yu-rong LIU
%J Journal of Zhejiang University SCIENCE B
%V 9
%N 4
%P 306~312
%@ 1673-1581
%D 2008
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0710625

T1 - A preliminary study on the teratogenesis of dexamethasone and the preventive effect of vitamin B12 on murine embryonic palatal shelf fusion in vitro
A1 - Sheng-jun LU
A1 - Wei HE
A1 - Bing SHI
A1 - Tian MENG
A1 - Xiao-yu LI
A1 - Yu-rong LIU
J0 - Journal of Zhejiang University Science B
VL - 9
IS - 4
SP - 306
EP - 312
%@ 1673-1581
Y1 - 2008
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0710625

Excessive dexamethasone (Dex) administrated into pregnant mice during critical periods of palatal development can produce a high incidence of cleft palate. Its mechanisms remain unknown. vitamin B12 has been shown to antagonize the teratogenic effects of Dex, which, however, remains controversial. In this study, we investigated the effects of Dex and vitamin B12 on murine embryonic palatal shelf fusion using organ culture of murine embryonic shelves. The explanted palatal shelves on embryonic day 14 (E14) were cultured for 24, 48, 72 or 96 h in different concentrations of Dex and/or vitamin B12. The palatal shelves were examined histologically for the morphological alterations on the medial edge epithelium (MEE) and fusion rates among different groups. It was found that the palatal shelves were not fused at 72 h or less of culture in Dex group, while they were completely fused in the control and vitamin B12-treated groups at 72 and 96 h, respectively. The MEE still existed and proliferated. In Dex+vitamin B12 group the palatal shelves were fused at each time point in a similar rate to controls. These results may suggest that Dex causes teratogenesis of murine embryonic palatal shelves and vitamin B12 prevents the teratogenic effect of Dex on palatogenesis on murine embryos in vitro.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Abbott, B.D., Birnbaum, L.S., 1990a. TCDD-induced altered expression of growth factors may have a role in producing cleft palate and enhancing the incidence of clefts after coadministration of retinoic acid and TCDD. Toxicol. Appl. Pharmacol., 106(3):418-432.

[2] Abbott, B.D., Birnbaum, L.S., 1990b. Rat embryonic palatal shelves respond to TCDD in organ culture. Toxicol. Appl. Pharmacol., 103(3):441-451.

[3] Abbott, B.D., Birnbaum, L.S., 1990c. Retinoic acid-induced alterations in the expression of growth factors in embryonic mouse palatal shelves. Teratology, 42(6):597-610.

[4] Abbott, B.D., Diliberto, J.J., Birnbaum, L.S., 1989a. 2,3,7,8-tetrachlorodibenzo-p-dioxin alters embryonic palatal medial epithelial cell differentiation in vitro. Toxicol. Appl. Pharmacol., 100(1):119-131.

[5] Abbott, B.D., Harris, M.W., Birnbaum, L.S., 1989b. Etiology of retinoic acid-induced cleft palate varies with the embryonic stage. Teratology, 40(6):533-553.

[6] Abbott, B.D., Diliberto, J.J., Birnbaum, L.S., 1992. Mechanisms of TCDD-induction of cleft palate: insights from in vivo and in vitro approaches. Chemosphere, 25(1-2):75-78.

[7] Abbott, B.D., Buckalew, A.R., DeVito, M.J., David R.P., Bryant, L., Schmid, J.E., 2003. EGF and TGF-α expression influence the developmental toxicity of TCDD: dose response and AhR phenotype in EGF, TGF-α, and EGF+TGF-α knockout mice. Toxicol. Sci., 71(1):84-95.

[8] Abbott, B.D., Best, D.S., Narotsky, M.G., 2005a. Teratogenic effects of retinoic acid are modulated in mice lacking expression of epidermal growth factor and transforming growth factor-alpha. Birth Defects Research Part A Clinical and Molecular Teratology, 73(4):204-217.

[9] Abbott, B.D., Buckalew, A.R., Leffler, K.E., 2005b. Effects of epidermal growth factor (EGF), transforming growth factor (TGF), and 2,3,7,8-tetrachlorodibenzo-p-dioxin on fusion of embryonic palates in serum-free organ culture using wild-type, EGF knockout, and TGF-α knockout mouse strains. Birth Defects Research Part A Clinical and Molecular Teratology, 73(6):447-454.

[10] Bock, K.W., Köhle, C., 2006. Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions. Biochem. Pharmacol., 72(4):393-404.

[11] Botto, L.D., Richard, S.J., Erickson, D., 2004. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am. J. Med. Genet. Part C: Semin. Med. Genet., 125C(1):12-21.

[12] Carmichael, S.L., Shaw, G.M., Ma, C., Werler, M.M., Rasmussen, S.A., Lammer, E.J., 2007. Maternal corticosteroid use and orofacial clefts. Am. J. Obstet. Gynecol., 197(6):585.e1-585.e7.

[13] Chou, M.J., Kosazuma, T., Takigawa, T., Yamada, S., Takahara, S., Shiota, K., 2004. Palatal shelf movement during palatogenesis: a fate map of the fetal mouse palate cultured in vitro. Anat. Embryol., 208(1):19-25.

[14] Degitz, S.J., Morris, D., George L., Foley, B., Francis, M., 1998. Role of TGF-β in RA-induced cleft palate in CD-1 mice. Teratology, 58(5):197-204.

[15] Greene, R.M., Kochhar, D.M., 1975. Some aspects of corticosteroid-induced cleft palate: a review. Teratology, 11(1):47-55.

[16] Gritli-Linde, A., 2007. Molecular control of secondary palate development. Dev. Biol., 301(2):309-326.

[17] Hackney, J.F., 1980. A glucocorticoid receptor in fetal mouse: its relationship to cleft palate formation. Teratology, 21(1):39-51.

[18] Hassell, J.R., 1975. The development of rat palatal shelves in vitro: An ultrastructural analysis of the inhibition of epithelial cell death and palate fusion by the epidermal growth factor. Dev. Biol., 45(1):90-102.

[19] Hassoun, E.M., Dencker, L., 1982. TCDD embryo toxicity in the mouse may be enhanced by β-naphthoflavone, another ligand of the Ah-receptor. Toxicol. Lett., 12(2-3):191-198.

[20] Herrmann, M., Schmidt, J., Umanskaya, N., Colaianni, G., Al Marrawi, F., Widmann, T., Zallone, A., Wildemann, B., Herrmann, W., 2007. Stimulation of osteoclast activity by low B-vitamin concentrations. Bone, 41(4):584-591.

[21] Koch, W.E., Smiley, G.R., 1981. In-vivo and in-vitro studies of the development of the avian secondary palate. Arch. Oral Biol., 26(3):181-187.

[22] Krapels, I.P.C., van Rooij, I.A.L.M., Ocké, M.C., van Cleef, B.A.G.L., Kuijpers-Jagtman, A.M., Steegers-Theunissen, R.P.M., 2004. Maternal dietary B vitamin intake, other than folate, and the association with orofacial cleft in the offspring. Eur. J. Nutr., 43(1):7-14.

[23] Kusanagi, T., 1984. Sensitive stages and dose-response analyses of palatal slit and cleft palate in C57BL/6 mice treated with a glucocorticoid. Teratology, 29(2):281-286.

[24] Miettinen, H.M., Huuskonen, H., Partanen, A.M., Miettinen, P., Tuomisto, J.T., Pohjanvirta, R., Tuomisto, J., 2004. Effects of epidermal growth factor receptor deficiency and 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal development in mice. Toxicol. Lett., 150(3):285-291.

[25] Montenegro, M.A., Palomino, H., 1989. Inhibition of palatal fusion in vitro by indomethacin in two strains of mice with different H-2 backgrounds. Arch. Oral Biol., 34(12):949-955.

[26] Natsume, N., Narukawa, T., Kawai, T., 1986. Teratogenesis of dexamethasone and preventive effect of vitamin B12. Int. J. Oral Maxillofac. Surg., 15(6):752-755.

[27] Newall, D.R., Edwards, J.R.G., 1981. The effect of vitamin A on fusion of mouse palates. I. Retinyl palmitate and retinoic acid in vivo. Teratology, 23(1):115-124.

[28] Nugent, P., Ma, L., Greene, R.M., 1998. Differential expression and biological activity of retinoic acid-induced TGFβ isoforms in embryonic palate mesenchymal cells. J. Cell. Physiol., 177(1):36-46.

[29] Pourtois, M., 1966. Onset of the acquired potentiality for fusion in the palatal shelves of rats. J. Embryol. Exp. Morphol., 16(1):171-182.

[30] Pratt, R.M., Perry, E.L., Chapman, L.M., Goulding, E.H., 1984. Glucocorticoid teratogenesis in mouse whole embryo culture. Teratology, 30(1):71-81.

[31] Rice, D.P., 2005. Craniofacial anomalies: from development to molecular pathogenesis. Curr. Mol. Med., 5(7):699-722.

[32] Ryan, R.P., Sunahara, G.I., Lucier, G.W., Birnbaum, L.S., Nelson, K.G., 1989. Decreased ligand binding to the hepatic glucocorticoid and epidermal growth factor receptors after 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7, 8-hexachlorodibenzofuran treatment of pregnant mice. Toxicol. Appl. Pharmacol., 98(3):454-464.

[33] Selhub, J., 2002. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J. Nutr. Health Aging, 6(1):39-42.

[34] Shah, R.M., Chen, Y.P., Burdett, D.N., 1989. Growth of the secondary palate in the hamster following hydrocortisone treatment: shelf area, cell number, and DNA synthesis. Teratology, 40(2):173-180.

[35] Shimizu, N., Aoyama, H., Hatakenaka, N., Kaneda, M., Teramoto, S., 2001. An in vitro screening system for characterizing the cleft palate-inducing potential of chemicals and underlying mechanisms. Reprod. Toxicol., 15(6):665-672.

[36] Stoll, C., Dott, B., Alembik, Y., Koehl, C., 1999. Maternal trace elements, vitamin B12, vitamin A, folic acid, and fetal malformations. Reprod. Toxicol., 13(1):53-57.

[37] van Rooij, I.A., Swinkels, D.W., Blom, H.J., Merkus, H.M., Steegers-Theunissen, R.P., 2003. Vitamin and homocysteine status of mothers and infants and the risk of nonsyndromic orofacial clefts. Am. J. Obstet. Gynecol., 189(4):1155-1160.

[38] Vargas, V.I., 1967. Palatal fusion in vitro in the mouse. Arch. Oral Biol., 12(11):1283-1288.

[39] Vujkovic, M., Ocke, M.C., van der Spek, P.J., Yazdanpanah, N., Steegers, E.A., Steegers-Theunissen, R.P., 2007. Maternal western dietary patterns and the risk of developing a cleft lip with or without a cleft palate. Obstet. Gynecol., 110(2 Pt 1):378-384.

[40] Weingärtner, J., Maile, S., Proff, P., Reicheneder, C., Bienengräber, V., Fanghänel, J., Gedrange, T., 2007. Secondary palatal closure in rats in association with relative maternofetal levels of folic acid, vitamin B12, and homocysteine. Ann. Anat., 189(3):229-233.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE