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

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 beta1 (TGF-a/beta1), and TGF-beta1 receptor type I (TbetaR-I) and type II (TbetaR-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.

Expression and regulation of plasminogen activators, plasminogen activator inhibitor type-1, and steroidogenic acute regulatory protein in the rhesus monkey corpus luteum.

The corpus luteum (CL) is a transient endocrine organ that secretes progesterone to support early pregnancy. Using primate materials obtained from rhesus monkeys, we have in this study investigated the expression and regulation of the plasminogen activators (PAs) and PA inhibitor type 1 (PAI-1) during CL development and regression. Adult (5-7 yr old) female rhesus monkeys were treated with pregnant mare serum gonadotropin/human chorionic gonadotropin to induce ovulation and follicular luteinization.

Regulatory effect of IFN-gamma on expression of TGF-beta 1, T beta R-II, and StAR in corpus luteum of pregnant rhesus monkey.

Aim: To examine expression of transforming growth factor-beta 1 (TGF-beta 1) and TGF beta receptor II (T beta R-II) and steroidogenic acute regulatory protein (StAR) in the corpus luteum (CL) of pregnant monkeys at various stages and to study possible effect of IFN-gamma on their production.

Methods: In situ hybridization and immunohistochemistry were applied to detect mRNA and protein.

Results: The expression of StAR, TGF-beta 1, and T beta R-II in the pregnant monkey CL was progressively decreased from d 15 to d 35 of gestation.