Insulin-like growth factor and insulin-like growth factor-binding proteins in the bovine uterus throughout the oestrous cycle.

The aims of the present study were to assess several components of the insulin-like growth factor (IGF) system in bovine uterine flushings across different days of the oestrous cycle and to examine the relationship between the IGF system and systemic progesterone concentrations. Uterine flushings and plasma were collected from cows on Days 3, 7, 11 and 15 of the oestrous cycle. The IGF-1 concentration was more than 5-fold higher in the uterus compared with plasma on Days 7 and 11 of the cycle, with values similar on Days 3 and 15. Similarly, uterine concentrations of IGF-binding protein (IGFBP)-2 and IGFBP-3 were up to 10- and 4-fold higher than in plasma, respectively, suggesting synthesis and/or transportation of the IGFBPs into the uterus. In addition, concentrations of IGFBP-2 and IGFBP-3 were higher in the uterine horns, ipsilateral to the corpus luteum, on Day 15. This difference could indicate a local controlling mechanism with progesterone possibly playing a role in regulating the concentration of IGFBPs between the uterine horns. There was no significant relationship between systemic progesterone concentrations and IGFBP concentrations on Day 7 of the oestrous cycle. The present study shows that uterine concentrations of IGFBPs are cycle stage specific and also suggests IGF-dependent and -independent functions for IGFBPs during a time of major change in the developing embryo.

Retinol-binding protein (RBP), retinol and ß-carotene in the bovine uterus and plasma during the oestrous cycle and the relationship between systemic progesterone and RBP on day 7.

In the dairy cow, low systemic concentrations of progesterone are known to be a major factor associated with early embryo loss. Endometrial expression of the gene encoding retinol-binding protein (RBP) is sensitive to small changes in progesterone on day 7 of the oestrous cycle. The objectives of the present study were to measure RBP concentrations in bovine uterine flushings and plasma across different days of the oestrous cycle and to examine the relationship between uterine RBP and systemic concentrations of progesterone. Uterine flushings and plasma were collected from cows on days 3, 7, 11 and 15 of the oestrous cycle. Uterine RBP concentrations were five- to 15-fold higher (P < 0.001) on day 15 compared with the other days and twofold higher (P < 0.001) in the uterine horn ipsilateral to the corpus luteum on day 15. RBP concentrations were similar in flushings and plasma across days 3-11; however, day 15 RBP concentrations were six- to 15-fold higher (P < 0.001) in uterine flushings. No significant relationship was found between the concentration of systemic progesterone and RBP concentrations on day 7. Overall, the results of the present study indicate a local controlling mechanism operating at the level of the endometrium to regulate RBP secretion, most likely progesterone.

Bolus delivery of mesenchymal stem cells to injured vasculature in the rabbit carotid artery produces a dysfunctional endothelium.

Endothelial dysfunction is an important factor in cardiovascular pathology. It has been suggested that pluripotent mesenchymal stem cells (MSCs) may contribute to repair of the endothelium through paracrine pathways. Enhanced re-endothelialization may be associated with a better outcome following angioplasty procedures. We examined the effect of the delivery of MSCs to a denuded vessel in vivo. The right carotid arteries of New Zealand white rabbits were denuded using an uninflated 3-French Fogarty balloon catheter. 1 x 10(5) MSCs in a bolus of 150 microL were then delivered intraluminally and allowed to dwell for 20 min. MSC engraftment was assessed using PKH-26 labeling and transduction with adenoviral reporter genes. Vessels were examined at 2 weeks for levels of endothelialization, as well as for neointimal hyperplasia and vasomotor function. Engraftment of MSCs was noted in the vessel wall following local arterial delivery. Endothelialization was improved following bolus MSC delivery at 2 weeks post-intervention. However, this endothelium is manifestly dysfunctional as indicated by a significant impairment in vasomotor activity and a significant increase in neointimal formation post-bolus delivery. Consistent with the formation of a dysfunctional endothelium, there was a higher rate of vessel occlusions in bolus-treated vessels due to not only predominately thrombosis but also neointimal hyperplasia. Our results suggest that naive MSCs delivered as a bolus to the occluded injured vascular segment generate dysfunctional endothelium presenting a risk of vessel occlusion. Such risks are important and need to be further assessed.