Influence of the angiotensinogen gene on the ovulatory capacity of mice

Objective: The tissue-bound ovarian renin-angiotensin system (OVRAS) is critically involved in ovulation in humans and rodents. Mice with disruption and overexpression of the angiotensinogen gene ( Agt) have been previously generated. We investigated the influence of varying Agt gene expression on the 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 Agt (one copy: n = 48; two copies: 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 development of zygotes, evaluation of ovarian histology, serum estradiol measurements. Result(s): The mean number of oocytes harvested was greatest in wild-type mice (two copies of Agt, 39.9 ± 14) with a reduction of ovulatory capacity 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 decrease of ovulatory capacity compared to wild-type mice (35.8 ± 15.2, P = .29). Ovarian histology, serum estradiol levels, and early embryonic development 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.