Angiopoietin-1 and -2 mRNA and protein expression in mouse preimplantation embryos and uteri suggests a role in angiogenesis during implantation
A. P. Hess A B C , J. Hirchenhain B , A. Schanz B , S. Talbi A , A. E. Hamilton A , L. C. Giudice A and J. S. Krüssel BA Department of Gynecology and Obstetrics, Stanford University Medical School, 300 Pasteur Drive, Stanford, CA, 94305-5317 USA.
B Department of Gynecology and Obstetrics, Heinrich-Heine-University Medical Center, Düsseldorf, Germany.
C Corresponding author. Email: alexandrahess2005@yahoo.de
Reproduction, Fertility and Development 18(5) 509-516 https://doi.org/10.1071/RD05110
Submitted: 15 September 2005 Accepted: 24 January 2006 Published: 8 May 2006
Abstract
After attachment and migration through the endometrial epithelium, the embryo must induce angiogenesis within the endometrial stroma to successfully complete the implantation process. Growth factors have been shown to play an important role in embryo implantation and placentation. The aim of the study was to investigate the expression of angiopoietin-1 and -2 (Ang-1 and -2) mRNA and protein expression during the development of single preimplantation mouse embryos and of possible complementary expression in mouse uteri. Angiopoietin-1 mRNA was expressed throughout development in 78% of zygotes, 66% of 2-cell-embryos, 71% of 4-cell-embryos, 70% of 8-cell-embryos, 60% of morula stages, 48% of early blastocysts and 78% of late blastocysts. The number of Ang-1-expressing embryos in the early-blastocyst group was significantly different in comparison with zygotes, 4-cell-embryos, 8-cell-embryos and late blastocysts. Angiopoietin-2 mRNA and protein expression could not be detected in preimplantation embryos. Examination of the uteri revealed Ang-2 mRNA and protein expression in the oestrogen-dominated cycling phase and the progesterone-dominated mated phase, whereas Ang-1 expression was restricted to the mated phase. Herein, Ang-1 expression in preimplantation mouse embryos as well as Ang-1 and -2 expression in mouse uteri is demonstrated, suggesting a possible role for angiopoietins in the embryo–maternal dialogue of the implantation process via an enhancement of the vascular remodelling in favour of an implanting conceptus.
Extra keywords: embryo development, reverse transcription–polymerase chain reaction, uterus.
Adamson, S. L. , Lu, Y. , Whiteley, K. J. , Holmyard, D. , Hemberger, M. , Pfarrer, C. , and Cross, J. C. (2002). Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Dev. Biol. 250, 358–373.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Chakraborty, I. , Das, S. K. , and Dey, S. K. (1995). Differential expression of vascular endothelial growth factor and its receptor mRNAs in the mouse uterus around the time of implantation. J. Endocrinol. 147, 339–352.
| PubMed |
Kaye, P. L. (1997). Preimplantation growth factor physiology. Rev. Reprod. 2, 121–127.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kingdom, J. C. , and Kaufmann, P. (1997). Oxygen and placental villous development: origins of fetal hypoxia. Placenta 18, 613–621.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Koblizek, T. I. , Weiss, C. , Yancopoulos, G. D. , Deutsch, U. , and Risau, W. (1998). Angiopoietin-1 induces sprouting angiogenesis in vitro. Curr. Biol. 8, 529–532.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Krikun, G. , Sakkas, D. , Schatz, F. , Buchwalder, L. , Hylton, D. , Tang, C. , and Lockwood, C. J. (2000). Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammation. Biochem. Biophys. Res. Commun. 275, 159–163.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Krüssel, J. S. , Huang, H. Y. , Simon, C. , Behr, B. , Pape, A. R. , Wen, Y. , Bielfeld, P. , and Polan, M. L. (1998). Single blastomeres within human preimplantation embryos express different amounts of messenger ribonucleic acid for beta-actin and interleukin-1 receptor type I. J. Clin. Endocrinol. Metab. 83, 953–959.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Krüssel, J. S. , Casan, E. M. , Raga, F. , Hirchenhain, J. , Wen, Y. , Huang, H. Y. , Bielfeld, P. , and Polan, M. L. (1999). Expression of mRNA for vascular endothelial growth factor transmembraneous receptors Flt1 and KDR, and the soluble receptor sflt in cycling human endometrium. Mol. Hum. Reprod. 5, 452–458.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Krüssel, J. S. , Behr, B. , Hirchenhain, J. , Wen, Y. , Milki, A. A. , Cupisti, S. , Bielfeld, P. , and Polan, M. (2000). Expression of vascular endothelial growth factor mRNA in human preimplantation embryos derived from tripronuclear zygotes. Fertil. Steril. 74, 1220–1226.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Krüssel, J. S. , Behr, B. , Milki, A. A. , Hirchenhain, J. , Wen, Y. , Bielfeld, P. , and Polan, M. L. (2001). Vascular endothelial growth factor (VEGF) mRNA splice variants are differentially expressed in human blastocysts. Mol. Hum. Reprod. 7, 57–63.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Krüssel, J. S. , Bielfeld, P. , Polan, M. L. , and Simon, C. (2003). Regulation of embryonic implantation. Eur. J. Obstet. Gynecol. Reprod. Biol. 110(Suppl. 1), S2–S9.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kumazaki, T. , Hamada, K. , and Mitsui, Y. (1994). Detection of mRNA expression in a single cell by direct RT-PCR. Biotechniques 16, 1017–1019.
| PubMed |
Li, X. F. , Charnock-Jones, D. S. , Zhang, C. , Hiby, S. , and Malik, S. , et al. (2001). Angiogenic growth factor messenger ribonucleic acids in uterine natural killer cells. J. Clin. Endocrinol. Metab. 86, 1823–1834.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Neufeld, G. , Cohen, T. , Gengrinovitch, S. , and Poltorak, Z. (1999). Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 9–22.
| PubMed |
Papapetropoulos, A. , Garcia-Cardena, G. , Dengler, T. J. , Maisonpierre, P. C. , Yancopoulos, G. D. , and Sessa, W. C. (1999). Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab. Invest. 79, 213–223.
| PubMed |
Peters, K. G. (1998). Vascular endothelial growth factor and the angiopoietins: working together to build a better blood vessel. Circ. Res. 83, 342–343.
| PubMed |
Risau, W. (1997). Mechanisms of angiogenesis. Nature 386, 671–674.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Rossant, J. , and Cross, J. C. (2001). Placental development: lessons from mouse mutants. Nat. Rev. Genet. 2, 538–548.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Rothstein, J. L. , Johnson, D. , DeLoia, J. A. , Skowronski, J. , Solter, D. , and Knowles, B. (1992). Gene expression during preimplantation mouse development. Genes Dev. 6, 1190–1201.
| PubMed |
Sato, T. N. , Tozawa, Y. , Deutsch, U. , Wolburg-Buchholz, K. , Fujiwara, Y. , Gendron-Maguire, M. , Gridley, T. , Wolburg, H. , Risau, W. , and Qin, Y. (1995). Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376, 70–74.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Schultz, R. M. (1993). Regulation of zygotic gene activation in the mouse. Bioessays 15, 531–538.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Sharkey, A. M. , Dellow, K. , Blayney, M. , Macnamee, M. , Charnock-Jones, S. , and Smith, S. K. (1995). Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos. Biol. Reprod. 53, 974–981.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Shifren, J. L. , Tseng, J. F. , Zaloudek, C. J. , Ryan, I. P. , Meng, Y. G. , Ferrara, N. , Jaffe, R. B. , and Taylor, R. N. (1996). Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J. Clin. Endocrinol. Metab. 81, 3112–3118.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Smith, S. K. (2000). Angiogenesis and implantation. Hum. Reprod. 15(Suppl. 6), 59–66.
| PubMed |
Suri, C. , Jones, P. F. , Patan, S. , Bartunkova, S. , Maisonpierre, P. C. , Davis, S. , Sato, T. N. , and Yancopoulos, G. D. (1996). Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87, 1171–1180.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Torry, D. S. , Holt, V. J. , Keenan, J. A. , Harris, G. , Caudle, M. R. , and Torry, R. J. (1996). Vascular endothelial growth factor expression in cycling human endometrium. Fertil. Steril. 66, 72–80.
| PubMed |
Wulff, C. , Wilson, H. , Dickson, S. E. , Wiegand, S. J. , and Fraser, H. M. (2002). Hemochorial placentation in the primate: expression of vascular endothelial growth factor, angiopoietins, and their receptors throughout pregnancy. Biol. Reprod. 66, 802–812.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Yancopoulos, G. D. , Davis, S. , Gale, N. W. , Rudge, J. S. , Wiegand, S. J. , and Holash, J. (2000). Vascular-specific growth factors and blood vessel formation. Nature 407, 242–248.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Zhang, E. G. , Smith, S. K. , Baker, P. N. , and Charnock-Jones, D. S. (2001). The regulation and localization of angiopoietin-1, -2, and their receptor Tie2 in normal and pathologic human placentae. Mol. Med. 7, 624–635.
| PubMed |
