PARENT SESSION

(M496) WITHDRAWN.

Julio-Pieper, Marcela¹, Lara, Hernán¹, Vantman, David¹, Miranda, Cristian¹, Alba, Francisco¹, Cortinez, Armando¹, Romero, Carmen¹, ¹ Universidad de Chile, Santiago, Chile

ABSTRACT- Infertility disorders such as ovarian hyperstimulation syndrome, pregnancy loss and ovarian tumours, are commonly associated to defects in ovarian angiogenesis. The nerve growth factor (NGF) has shown to promote angiogenesis in several tissues and delayed wound healing has been associated with an impairment in the production of this neurotrophin. Although NGF is involved in a variety of ovarian functions, the effects of NGF on ovarian angiogenesis remain unexplored. The aim of this work was to elucidate if this neurotrophin has a role in ovarian expression of the angiogenic factors VEGF and TGFbeta1. Neonatal rat ovaries cultured for two hours in presence of NGF (100 ng/ml) had a significant increase in the content of mRNA for two isoforms of VEGF (0.65±0.04 vs 0.45±0.07 arbitrary units in stimulated ovaries and controls respectively, for VEGF 120 and 0.76±0.03 vs 0.42±0.10 for VEGF 164, p<0.05). NGF did not affect the content of TGFbeta1 mRNA. The denervation of juvenile rat ovaries, which induces accumulation of NGF within the gland, was capable to increase the amount of VEGF-immunoreactivity in this tissue (H-score 45.8±3.7 vs 12.0<5.7 in controls, p<0.01). Consistent with that, human granulosa cells cultured with NGF (50 ng/ml) released 38% more VEGF into the culture media (p<0.005). TGFbeta1 remained unchanged in both experiments. The above results indicate that NGF increases the expression of VEGF in the ovary, which may be important in the maintenance of the follicular and luteal vasculature. This data also suggests that a disruption on NGF regulation could be a component in ovarian disorders related with impaired angiogenesis. This work was supported by Conicyt 4040059 and Fondecyt 1030661. Marcela Julio-Pieper is recipient of a fellowship from the Chilean Government for PhD studies (Conicyt 102241).

KEY WORDS: NGF, VEGF, ovary, angiogenesis