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.


METHODS
Observational study of genetically altered mice and their response to a superovulation protocol.


METHODS
Academic research institution.


METHODS
Mice with varying copy numbers of Agt (one copy: n = 48; two copies: n = 51; three copies: n = 20; four copies: n = 24).


METHODS
Superovulation protocol, oocyte culture.


METHODS
Number of oocytes harvested, early embryonic development of zygotes, evaluation of ovarian histology, serum estradiol measurements.


RESULTS
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.


CONCLUSIONS
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.
Hefler
L A
LA
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
Gregg
A R
AR
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D004958:Estradiol / Q000097:blood; D005260:Female; D018628:Gene Dosage; D051379:Mice; D008817:Mice, Mutant Strains; D010053:Ovary / Q000166:cytology; D010060:Ovulation / Q000235:genetics*; D013480:Superovulation; D015053:Zygote / Q000502:physiology
D000808:Angiotensinogen; D004958:Estradiol