Involvement of molecules related to angiogenesis, proteolysis and apoptosis in implantation in rhesus monkey and mouse

Yi Xun Liu, Fei Gao, Peng Wei, Xin Lei Chen, Hong Juan Gao, Ru Jin Zou, Li Juan Siao, Fuhua Xu, Qing Feng, Kui Liu, Zhao Yuan Hu

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We have established the well-defined cycling, pseudo-pregnant and pregnant rhesus monkey models, and used these to analyze expression of the common molecules specifically related to angiogenesis, apoptosis or proteolysis, such as vascular endothelial growth factor (VEGF) and its receptors KDR, flt-1, flt-4 and flk-1, basic fibroblast growth factor (bFGF) and its receptors Flg, transforming growth factor-alpha and β1 (TGF-a/β1), and TGF-β1 receptor type I (TβR-I) and type II (TβR-II), as well as steroidogenic acute regulatory protein (StAR), tissue type plasminogen activator/urokinase plasminogen activator/plasminogen activator inhibitor type 1 (tPA/uPA/PAI-1) and matrix matalloproteinase type 1, -3/tissue inhibitor matalloproteinase type 1, -2, -3 (MMP-1, -3/TIMP-1, -2, -3), Fas/FasL, BcL-2/Bax, in the corpus luteum (CL), in the functional layer of the endometrium and in the materno-fetal boundary of the implantation site. We have demonstrated that:expression of these molecules in the monkey CL, endometrium and materno-fetal boundary of the implantation site is correlated well with CL functional and vascular development and with the processes involved in the establishment of the implantation window as well as with the early stages of placentation.a coordinated increase in tPA and its inhibitor PAI-1 expression in the monkey and rat CL may be instrumental in initiating luteal regression in both species, and correlated well with the timing of the closure of the implantation window, whereas high uPA activity in the CL is important for the early formation of the CL and for maintaining its function which is closely correlated to the period of establishment of the implantation window.apoptosis, proteolysis and angiogenesis occur in the CL and in the endometrium during the time of establishment of the implantation window, as well as in the materno-fetal boundary of the implantation site at the early stages of placentation. It seems that these processes occur in these tissues in a coordinated and time- and cell-dependent manner, and are reliant on each other. Based on these observations, we have designed experiments to test the actions of some related available compounds on mouse implantation, used alone or in combination. The preliminary data showed that the compounds which could effectively affect apoptosis, angiogenesis or proteolysis in the implantation site were capable of effectively inhibiting implantation by acting on the endometrium and/or on the CL. Furthermore, the combined use of these compounds produced an obvious additive effect on inhibiting implantation. This finding suggested this may be a good approach for developing an anti-implantation agent.

Original languageEnglish (US)
Pages (from-to)249-262
Number of pages14
JournalContraception
Volume71
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Corpus Luteum
Macaca mulatta
Proteolysis
Apoptosis
Endometrium
Plasminogen Activator Inhibitor 1
Placentation
Haplorhini
Vascular Endothelial Growth Factor Receptor-3
Luteolysis
Tissue Inhibitor of Metalloproteinase-2
Fibroblast Growth Factor Receptors
Transforming Growth Factor alpha
Vascular Endothelial Growth Factor Receptor
Tissue Inhibitor of Metalloproteinase-1
Plasminogen Activators
Urokinase-Type Plasminogen Activator
Fibroblast Growth Factor 2
Tissue Plasminogen Activator
Matrix Metalloproteinases

Keywords

  • Angiogenesis
  • Apoptosis
  • Endometrium
  • Implantation site
  • Proteolysis
  • Rhesus monkey

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Involvement of molecules related to angiogenesis, proteolysis and apoptosis in implantation in rhesus monkey and mouse. / Liu, Yi Xun; Gao, Fei; Wei, Peng; Chen, Xin Lei; Gao, Hong Juan; Zou, Ru Jin; Siao, Li Juan; Xu, Fuhua; Feng, Qing; Liu, Kui; Hu, Zhao Yuan.

In: Contraception, Vol. 71, No. 4, 04.2005, p. 249-262.

Research output: Contribution to journalArticle

Liu, YX, Gao, F, Wei, P, Chen, XL, Gao, HJ, Zou, RJ, Siao, LJ, Xu, F, Feng, Q, Liu, K & Hu, ZY 2005, 'Involvement of molecules related to angiogenesis, proteolysis and apoptosis in implantation in rhesus monkey and mouse', Contraception, vol. 71, no. 4, pp. 249-262. https://doi.org/10.1016/j.contraception.2004.12.008
Liu, Yi Xun ; Gao, Fei ; Wei, Peng ; Chen, Xin Lei ; Gao, Hong Juan ; Zou, Ru Jin ; Siao, Li Juan ; Xu, Fuhua ; Feng, Qing ; Liu, Kui ; Hu, Zhao Yuan. / Involvement of molecules related to angiogenesis, proteolysis and apoptosis in implantation in rhesus monkey and mouse. In: Contraception. 2005 ; Vol. 71, No. 4. pp. 249-262.
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AU - Liu, Yi Xun

AU - Gao, Fei

AU - Wei, Peng

AU - Chen, Xin Lei

AU - Gao, Hong Juan

AU - Zou, Ru Jin

AU - Siao, Li Juan

AU - Xu, Fuhua

AU - Feng, Qing

AU - Liu, Kui

AU - Hu, Zhao Yuan

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N2 - We have established the well-defined cycling, pseudo-pregnant and pregnant rhesus monkey models, and used these to analyze expression of the common molecules specifically related to angiogenesis, apoptosis or proteolysis, such as vascular endothelial growth factor (VEGF) and its receptors KDR, flt-1, flt-4 and flk-1, basic fibroblast growth factor (bFGF) and its receptors Flg, transforming growth factor-alpha and β1 (TGF-a/β1), and TGF-β1 receptor type I (TβR-I) and type II (TβR-II), as well as steroidogenic acute regulatory protein (StAR), tissue type plasminogen activator/urokinase plasminogen activator/plasminogen activator inhibitor type 1 (tPA/uPA/PAI-1) and matrix matalloproteinase type 1, -3/tissue inhibitor matalloproteinase type 1, -2, -3 (MMP-1, -3/TIMP-1, -2, -3), Fas/FasL, BcL-2/Bax, in the corpus luteum (CL), in the functional layer of the endometrium and in the materno-fetal boundary of the implantation site. We have demonstrated that:expression of these molecules in the monkey CL, endometrium and materno-fetal boundary of the implantation site is correlated well with CL functional and vascular development and with the processes involved in the establishment of the implantation window as well as with the early stages of placentation.a coordinated increase in tPA and its inhibitor PAI-1 expression in the monkey and rat CL may be instrumental in initiating luteal regression in both species, and correlated well with the timing of the closure of the implantation window, whereas high uPA activity in the CL is important for the early formation of the CL and for maintaining its function which is closely correlated to the period of establishment of the implantation window.apoptosis, proteolysis and angiogenesis occur in the CL and in the endometrium during the time of establishment of the implantation window, as well as in the materno-fetal boundary of the implantation site at the early stages of placentation. It seems that these processes occur in these tissues in a coordinated and time- and cell-dependent manner, and are reliant on each other. Based on these observations, we have designed experiments to test the actions of some related available compounds on mouse implantation, used alone or in combination. The preliminary data showed that the compounds which could effectively affect apoptosis, angiogenesis or proteolysis in the implantation site were capable of effectively inhibiting implantation by acting on the endometrium and/or on the CL. Furthermore, the combined use of these compounds produced an obvious additive effect on inhibiting implantation. This finding suggested this may be a good approach for developing an anti-implantation agent.

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KW - Angiogenesis

KW - Apoptosis

KW - Endometrium

KW - Implantation site

KW - Proteolysis

KW - Rhesus monkey

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