Urinary gonadotrophins but not recombinant gonadotrophins reduce expression of VEGF120 and its receptors flt-1 and flk-1 in the mouse uterus during the peri-implantation period.

BACKGROUND: Ovarian stimulation in humans might affect the perinatal outcome and be considered as a stress factor in the implantation process. In this study we compared the effects of recombinant and urinary gonadotrophins during the mouse peri-implantation period. METHODS: Adult female CD1 mice were treated as follows (a) urinary hFSH and urinary hCG, (b) recombinant hFSH and recombinant hLH and (c) saline. The effects of the gonadotrophins on the expression of vascular endothelial growth factor120 (VEG120) and its receptors and the corticotrophin releasing hormone (CRH) system during the peri-implantation period were studied. The specific effects of the different gonadotrophins on the onset of implantation were also studied. RESULTS: Urinary gonadotrophin treatment caused lower levels of VEGF120, flt-1 and flk-1 mRNA levels, reduced the size of the embryo implantation site, delayed implantation and prolonged the gestational period. Both urinary hFSH and urinary hCG contributed to the adverse effects. Levels of CRH and CRHR1 expression were not influenced. Recombinant gonadotrophin treatment did not alter any of the parameters studied. CONCLUSIONS: Our results show that the VEGF system of the mouse uterus during the peri-implantation period is adversely affected by urinary gonadotrophins but not by recombinant gonadotrophins. The CRH system was not affected by the two types of gonadotrophins.

Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis.

Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endothelial cells and may affect vascular morphogenesis via intracellular signaling, but the nature of these signals remains unknown. Here, targeted inactivation (VEC-/-) or truncation of the beta-catenin-binding cytosolic domain (VECdeltaC/deltaC) of the VE-cadherin gene was found not to affect assembly of endothelial cells in vascular plexi, but to impair their subsequent remodeling and maturation, causing lethality at 9.5 days of gestation. Deficiency or truncation of VE-cadherin induced endothelial apoptosis and abolished transmission of the endothelial survival signal by VEGF-A to Akt kinase and Bcl2 via reduced complex formation with VEGF receptor-2, beta-catenin, and phosphoinositide 3 (PI3)-kinase. Thus, VE-cadherin/ beta-catenin signaling controls endothelial survival.

The early development of the tunica media in the vascular system of rat embryos.

The use of a monoclonal antibody (HHF-35) against muscle-cell-specific actin has led to new insights into the early development and differentiation of the tunica media of blood vessels. The localization of this substance was studied by light and electron microscopy, in 22 rat embryos ranging between 10 and 15 days post coitum. Actin expression was already seen in the mesoderm around the dorsal aortae at 10 days post coitum, i.e. 1.5 day before circular mesenchymal condensations were detectable by light microscopy. These condensations are usually regarded as the first indication of arterial tunica media formation. The actin expression starts in the dorso-medial mesoderm surrounding the dorsal aortae at the level of the developing pharyngeal arch system, followed at 11.5 days by positive cells in the lateral mesoderm. In 12-day-old embryos most of the mesenchymal cells around the dorsal aortae contain actin, except for those aspects of the dorsal aortae which participate in outgrowing and connecting vessels to specific organs, such as the pharyngeal arch arteries, dorsal intersegmental arteries and aorto-pulmonary plexus, which themselves are still negative. At this stage the vitelline and umbilical arteries, which belong to the early developing ventral segmental arteries, are already surrounded by actin-containing mesenchymal cells. From 13 days onwards the tributary arteries, such as the subclavian and vertebral arteries, start to present the first differentiation of a tunica media in a proximo-distal development. In general the actin-negative areas are involved in vascular remodelling, implying the formation of new vessels, as as well as the disappearance of those previously developed.(ABSTRACT TRUNCATED AT 250 WORDS)

The special status of the pulmonary arch artery in the branchial arch system of the rat.

A renewed study of the development of the branchial arch system was essential in view of the special morphologic characteristics of the ductus arteriosus, which derives from the pulmonary arch artery or sixth branchial arch artery. In congenital heart disease certain aorto-pulmonary collateral arteries have a marked histological similarity to the ductus arteriosus. To gain a better insight into the development of these vessels, 27 rat embryos, with the number of somites ranging between 19 and 41, were studied. Most embryos were collected after shortterm in vitro-culture, allowing precise staging of age and development. The vascular system of these embryos was injected with Indian ink, to enable easy recognition of even the smallest endothelium-lined vessels. The embryos were serially sectioned (3-5 microns) and reconstructed using a graphic method. The results show that the pulmonary arch artery differs from the other arch arteries in that it is the most cranial vessel of a system of ventral splanchnic arteries, which connects the pulmonary plexus with the dorsal aortae at an early stage. With the exception of the pulmonary arch artery, these connections are transient. The pulmonary arteries develop from the remaining parts of the plexus. It is argued that these connections can persist in the human as aorto-pulmonary collaterals, in certain cases with abnormalities in the pulmonary part of the cardiac outflow tract.