The Role of Angiotensin II in Bovine Follicular Growth.

Angiotensin II (AngII) is involved in the control of some reproductive events in females. In cattle, AngII has a pivotal effect in ovulation and prevents the inhibitory effect of follicular cells on bovine oocyte nuclear maturation. The role of AngII in follicular growth has been studied only in rats, and it induces apoptosis in granulosa cells and atresia of antral follicles. However, some recent studies have shown that the expression of type 2 AngII receptors (AT2) is higher in healthy compared with atretic bovine follicles, and that FSH stimulates expression of AT2 in cultured bovine granulosa cells. The aim of this work was to investigate the role of AngII in bovine follicular growth using an in vivo model, through intrafollicular injection of AngII or AngII receptor antagonist. Cows were pre-synchronized to induce a new follicular wave and when the follicles reached 7-8mm diameter a single follicle was injected with saline, AngII or antagonist. Thereafter, all follicles were monitored by ultrasonography until 96 hours after intrafollicular injection. Follicles injected with saline solution (control group) reached ovulatory size and ovulated after GnRH agonist challenge, showing that the procedure did not affect follicular growth. The intrafollicular application of 10μM of saralasin (AngII-receptor blocker) inhibited follicular growth in all treated cows (4/4; P<0.01), showing that AngII is essential for follicular growth in 7-8mm follicles. However, injection of AngII did not affect follicular growth, and the pattern of follicular dynamics was similar to cows treated with saline (P>0.05), suggesting that follicles contain sufficient AngII for follicle development. To determine if AngII plays a pivotal role in selection of the dominant follicle, the second largest follicle was injected with AngII after follicle deviation. This AngII injection did not induce a codominant follicle (0/4 cows) and the injected follicles had lower growth rate than the dominant follicle (P<0.001). These results suggest that AngII alone does not induce follicle dominance and probably interacts with gonadotropins and growth factors to determine follicular development. A third experiment was performed to test the hypothesis that AngII is essential for follicular growth during the gonadotropin-independent period. Saralasin was injected and the cows were or were not treated with systemic FSH (every 12h for 96h). FSH overcame the negative effect of saralasin on follicular growth (P<0.05) and all cows (3/3) ovulated at 120h after treatments. These results demonstrated that AngII plays a role in growth of 7-8mm follicles and evidence that AngII is not essential for all stages of follicular development but mainly during the gonadotropin-independent period. Supported by CAPES and CNPq, Brazil.