In this regard, members of the Bcl2 gene family have been described as main participants in the cascade of events that activate or inhibit apoptosis. The BCL2-related proteins can be separated into anti- and proapoptotic members, and the balance between these counteracting proteins presumably determines cell fate. In our experimental model, antral follicles obtained from Trap-treated rats showed a decrease in BCL2 and an increase in BAX protein levels. In addition, a reduction in the BCL2L1l:BCL2L1s ratio was observed in this group, with a reduction of BCL2L1L greater than that of BCL2L1S, showing that the expression of these antiapoptotic proteins is lower in follicles from intraovarian Trap-treated rats.
In conclusion, the inhibition of VEGFA activity appears to produce an increase in ovarian apoptosis through an imbalance in the ratio of antiapoptotic:proapoptotic proteins, leading a larger number of follicles to atresia. The mechanism could take place either through an increase in blood vessel extension or through a direct effect mediated by an ovarian VEGFA receptor in granulosa cells. Further information is needed to elucidate the relevance of the changes observed in the vasculature during folliculogenesis and to define the regulations and clarify the interactions between VEGFA and the hormones essential for normal ovarian function. Therefore, VEGFA would be a major limiting factor for follicular development and atresia.
The antiapoptotic actions of VEGFA in the ovary put this factor in a new position as one whose abnormal expression may lead to many diseases caused by dysregulations of programmed cell death. Moreover, the results described in the present study may provide insight into the mechanisms by which VEGFA has an effect on ovarian disorders (such as polycystic ovary syndrome and ovarian hyperstimulation syndrome). In addition, the use of antiangiogenic compounds may contribute to the development of new therapeutic strategies.