Influence of the angiotensinogen gene on the ovulatory capacity of mice

Objective: The tissue-bound ovarian renin-angiotensin system (OVRAS) is cri tically involved in ovulation in humans and rodents, Mice with disruption a nd overexpression of the angiotensinogen gene (Agt) have been previously ge nerated. We investigated the influence of varying Agr gene expression on th e ovulatory capacity and early embryonic development in mice. Design: Observational study of genetically altered mice and their response to a superovulation protocol. Setting: Academic research institution. Animal(s): Mice with varying copy numbers of Agr (one copy: n = 48; two cop ies: n = 51, three copies: n = 20; four copies: n = 24). Intervention(s): Superovulation protocol, oocyte culture. Main Outcome Measure(s): Number of oocytes harvested, early embryonic devel opment of zygotes, evaluation of ovarian histology, serum estradiol measure ments. Result(s): The mean number of oocytes harvested was greatest in wild-type m ice (two copies of Agt, 39.9 +/- 14) with ct reduction of ovulatory capacit y in mice overexpressing Agt (three copies [34.8 +/- 11.7] and four copies [31.2 +/- 12.4], P = .026). Mice with one copy of Agt showed a slight decre ase of ovulatory capacity compared to wild-type mice (35.8 +/- 15.2, P = .2 9). Ovarian histology, serum estradiol levels, and early embryonic developm ent were independent of the Agt genotype. Conclusion(s): Overexpression of Agt was associated with reduced ovulatory capacity, but with none of the other parameters that were evaluated. These findings support an important role of the ovarian renin-angiotensin system in the process of follicular rupture. (Fertil Steril(R) 2001,75:1206-11. (C ) 2001 by American Society for Reproductive Medicine.).