The Expressions of P53, MDM2 in Trophoblasts of Spontaneous Abortion Mouse Model and the Relevant Researches

Abstract

Objective: To explore the mRNA expression of the related genes of p53, MDM2, vascular endothelial growth factor (VEGF) and hypoxia inducible transcription factors-1 a (HIF-la) in villous samples of spontaneous abortion mouse models and normal pregnancy models, and to discuss the effect of p53, MDM2 on the growth of villous trophoblast cells. Methods: The abortion-prone CBAXDBA/2 matings were established as the model of spontaneous abortion and the non-abortion-prone CBAXBALB/c matings as the model of normal pregnancy. Applied q Real-time PCR method to detect the mRNA expression levels of p53, MDM2, VEGF and HIF-la in villous samples of spontaneous abortion mouse models and normal pregnancy models. Results: The relationship of the mRNA expression level of p53, MDM2, VEGF and HIF-la in vinous samples of spontaneous abortion mouse models: in the villous samples of spontaneous abortion mouse models, the expression of p53 was positively correlated with the expression of MDM2, HIF-la (r = 0.35; r = 0.63), and the relationship was significant (P = 0.01; P < 0.001); but negatively correlated to the expression of VEGF (r = ?0.30), and the relationship was significant (P = 0.03). The expression of MDM2 was positively correlated with the expression of HIF-la (r = 0.28), and the relationship was significant (P = 0.04); and negatively correlated with the expression of VEGF (r = ?0.08), but the relationship was not significant (P = 0.57). The expression of HIF-la was negatively correlated with the expression of VEGF (r = ?0.37), and the relationship was significant (P = 0.007). The relationship of the mRNA expression level of p53,MDM2, VEGF and HIF-1 a in vinous samples of normal pregnancy models: in the vinous samples of normal pregnancy models, the expression of p53 was positively correlated with the expression of MDM2, VEGF and HIF-la (r = 0. 31; r = 0. 48; r = 0. 67), and the relationship was significant (P = 0.03; P = 0.003; P < 0.001). The expression of MDM2 was positively correlated with the expression of VEGF (r = 0. 23), but the relationship was not significant (P = 0.11); and negatively correlated with the expression of HIF-la (r = ?0.03), but the relationship was not significant (P = 0.84). The expression of HIF-la was positively correlated with the expression of VEGF (r = 0. 35), and the relationship was significant (P = 0.01). Conclusion: angiogenesis reduces in villous samples of spontaneous abortion mouse model, P53 and MDM2 involve in angiogenesis in villous samples, unlikely p53, and MDM2 have effects on normal early pregnancy villous angiogenesis and when the cell DNA damages or hypoxia exacerbates, it can induce high expression of p53, MDM2, inhibit angiogenesis in villous samples in early pregnancy. P53, MDM2 generegulate villous trophoblast cell growth by adjusting expression of HIF-1a and VEGF gene, finally influences pregnancy.

 

Share and Cite:

Zhou, C. , Wang, Q. , Zeng, M. , Cheng, L. and Xie, X. (2013) The Expressions of P53, MDM2 in Trophoblasts of Spontaneous Abortion Mouse Model and the Relevant Researches. Engineering, 5, 371-375. doi: 10.4236/eng.2013.510B075.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] M. Jerzak and P. Bischof, “Apoptosis in the First Trimester Human Placenta: The Role in Maintaining Privilege at the Matemal-Foetal Interface and the Trophoblast Remodeling,” The European Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 100, 2002, pp. 138- 142. http://dx.doi.org/10.1016/S0301-2115(01)00431-6
[2] D. Michael and M. Oren, “The p53-Mdm2 Module and the Ubiquitin System,” Cancer Biology, Vol. 13, 2003, pp. 49-58. http://dx.doi.org/10.1016/S1044-579X(02)00099-8
[3] G. Beckman, R. Birgander, A. Sjalander, et al., “Is p53 Polymorphism Maintained by Natural Selection?” Human Heredity, Vol. 44, 1994, pp. 266-270. http://dx.doi.org/10.1159/000154228
[4] L. V. J. Schaffer, C. Breymann, M. Gassmann and H. H. Marti, “Preserved Placental Oxygenation and Development during Severe Systemic Hypoxia,” The American Journal of Physiology Regulatory, Integrative and Comparative Physiology, Vol. 290, No. 3, 2006, pp. 844-851. http://dx.doi.org/10.1152/ajpregu.00237.2005
[5] A. C. K. Ajakumar, “Expression, Ontogeny, and Regulation of Hypoxia-Inducible Transcription Factors in the Human Placenta,” Biology of Reproduction, Vol. 63, No. 2, 2000, pp. 559-569. http://dx.doi.org/10.1095/biolreprod63.2.559
[6] D. E. F. J. Ingber, “Mechanochemical Switching between Growth and Differentiation during Fibroblast Growth Factor-Stimulated Angiogenesis in Vitro: Role of Extracellular Matrix,” The Journal of Cell Biology, Vol. 109, No. 1, 1989, pp. 317-330.
[7] M. D. L. D. Mueller, E. Garrett and R. N. Taylor, “Neutrophils Infiltrating the Endometrium Express Vascular Endothelial Growth Factor: Potential Role in Endometrial Angiogenesis,” Fertility and Sterility, Vol. 74, No. 1, 2000, pp. 107-112.
[8] S. SK, “Angiogenesis and Implantation,” Human Reproduction, Vol. 15, No. S6, 2000, pp. 59-66.
[9] L. O. A. Hefler, P. Husslein, C. Kainz and C. Tempfer, “Vascular Endothelial Growth Factor Serum Levels in Pregnancy and Preeclampsia,” Acta Obstetricia et Gynecologica Scandinavica, 2000, pp. 77-78.
[10] H. H. R. W. Marti, “Angiogenesis in Ischemic Disease,” Vol. 82, 1999, pp. 44-52.
[11] S. N. K. aishi, N. Kinukawa, H. Nakano and K. Sueishi, “Immunohistochemical Localization of Vascular Endothelial Growth Factor in the Human Placenta,” Placenta, Vol. 17, No. 2-3, 1996, pp. 111-121.
[12] P. C. O. Vuorela, M. Tulppala and E. Halmesmaki, “VEGF, Its Receptors and the Tie Receptors in Recurrent Miscarriage,” Molecular Human Reproduction, Vol. 6, No. 3, 2000, pp. 276-282.
[13] G. J. H. J. Burton and A. L. Wetson, “Maternal Arterial Connections to the Placectal Intervil Lous Space during the First Trimester of Human Pregnancy,” American Journal of Obstetrics & Gynecology, Vol. 181, 1999, p. 71.
[14] H. D. Z. J. Skinner, J. Fang, F. Agani and B. H. Jiang, “Vascular Endothelial Growth Factor Transcriptional Activation Is Mediated by Hypoxia-Inducible Factor Lalpha, HDM2, and p74S6K1 in Response to Phosphatidylinositol 3-Kinase/AKT Signaling,” The Journal of Biological Chemistry, Vol. 279, No. 44, 2004, pp. 45643-51.
[15] M. Thomas, A. Kalita, S. Labrecque, et al., “Two Polymorphic Variants of Wild-Type p53 Differ Biochemically and Biologically,” Molecular and Cellular Biology, 1999, pp. 1092-1100.
[16] P. Dumont, J. I. Leu, A. Cr. Della Pietra, et al., “The Codon 72 Polymorphic Variants of p53 Have Markedly Different Apoptotic Potential,” Nature Genetics, Vol. 33, 2003, pp. 357-365.
[17] G. L. Bond, W. Hu, E. E. Bond, et al., “A Single Nucleotide Polymorphism in the MDM2 Promoter Attenustes the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans,” Cell, Vol. 119, 2004, pp. 591- 602.
[18] D. Michael and M. Oren, “The p53-Mdm2 Module and the Ubiquitin System,” Cancer Biology, Vol. 13, 2003, pp. 49-58.
[19] Y. Hong, X. Zhang, et al., “The Role of p53 and MDM2 Polymorphisms in the Risk of Esophagel Squamaous Cell Carcinoma,” Cancer Research, Vol. 65, 2005, pp. 9582- 9587.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.