We will address, in this review, the role of angiotensin II (AngII) on follicular development and ovulation. Over the last few years, our research group has focused on studying the contribution of renin-angiotensin system in antral follicle development and ovulation and a new concept of local regulation has been established using cattle as a model. We previously demonstrated that AT1 and AT2 receptors are expressed in both granulosa and theca cells. The abundance of AT2 mRNA in granulosa cells was higher in healthy compared with atretic follicles, whereas both receptors in theca cells and AT1 in granulosa cells did not change. Granulosa cells cultured with hormones that stimulate estradiol secretion increased AT2 mRNA and protein levels, whereas fibroblast growth factors (FGF-7 and 10) inhibited estradiol secretion and AT2 protein levels. We also found that the concentration of AngII increases in dominant follicle at expected time for follicular deviation. Transvaginal ultrasound has been used for intrafollicular injection to understand the regulation of follicular wave and ovulation. With this in vivo model, we have demonstrated that AngII-receptor blocker inhibits follicular growth and decreases estradiol concentration in follicular fluid and downregulates mRNA expression of genes involved in follicular development. Moreover, intrafollicular injection of AngII or AT2-specific agonist prevented the expected atresia of the second largest follicle, which continued to grow at a rate similar to the dominant follicle for 24 h. These findings have provided evidence that AngII plays an important role in follicle development. In regarding to ovulation, we demonstrated that AngII antagonists block ovulation in cattle when intrafollicularly injected at 0 and 6 h after applying GnRH agonist. Ovulation was also inhibited by AT2- but not by AT1-AngII receptor antagonist. Furthermore, AngII stimulates an enhancement in mRNA abundance of genes involved in ovulation. In addition, AngII stimulates genes involved in extracellular remodeling and follicular wall rupture. In conclusion, our data from in vitro and in vivo studies have demonstrated that AngII plays a pivotal role in the antral follicle development and early mechanism of ovulation via the AT2 receptor subtype in cattle.
