Genetic contributions of the endothelial nitric oxide synthase gene to ovulation and menopause in a mouse model.
OBJECTIVE
To investigate the influence of the endothelial nitric oxide synthase gene (Nos3) on ovulatory capacity and reproductive senescence.


METHODS
Prospective, controlled study.


METHODS
Academic research institution.


METHODS
Laboratory mice with targeted mutagenesis of Nos3.


METHODS
Hyperstimulation protocol, oocyte culture, and ovarian histology using wild-type (Nos3(+/+); n = 20), heterozygous (Nos3(+/m); n = 39), and homozygous deficient (Nos3(m/m); n = 11) female mice; observation of reproductive outcomes.


METHODS
Number and survival of oocytes; onset of menarche and menopause.


RESULTS
The mean number of superovulated oocytes (18 +/- 36 vs. 41 +/- 4) and the 48-hour overall survival rate of embryos (65% vs. 81%) were significantly reduced for Nos3(m/m) female mice compared with Nos3(+/+) female mice. Nos3(m/m) females showed a significantly reduced number and size of antral follicles and corpora lutea compared with wild-type controls. Compared with Nos3(+/m) x Nos3(+/m) breedings, Nos3(m/m) x Nos3(m/m) breedings showed a higher female age at first litter (76.2 +/- 10.3 vs. 107.8 +/- 26.6 days), fewer litters (10.5 +/- 3.6 vs. 7. 8 +/- 4.2), and a lower female age at reproductive senescence (400.2 +/- 64.5 vs. 332.1 +/- 27.4 days), respectively.


CONCLUSIONS
Our data suggest that Nos3 deficiency is associated with reduced ovulatory capacity and impaired early embryonic viability and that it influences the onset of menarche and menopause.
Tempfer
C
C
University of Vienna, Vienna, Austria. clemens.tempfer@akh-wien.ac.at
Moreno
R M
RM
O'Brien
W E
WE
Gregg
A R
AR
D000375:Aging / Q000235:genetics; D000818:Animals; D004958:Estradiol / Q000097:blood; D005260:Female; D005838:Genotype; D008593:Menopause / Q000235:genetics*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009865:Oocytes / Q000201:enzymology / Q000254:growth & development; D010053:Ovary / Q000648:ultrastructure; D010060:Ovulation / Q000235:genetics*; D011446:Prospective Studies; D013480:Superovulation
D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse