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.