Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model.

Two consecutive experiments determined whether disruption of the endothelial nitric oxide synthases (NOS) gene (Nos3) affects ovulation, fertilization, implantation, and embryo development. In the first trial, Nos3-knockout mice (groups Nos3(-/-)) and wild-type mice (groups Nos3(+/+)) showed significant differences in mean number of corpora lutea (9.7+/-1.2 in Nos3(-/-) versus 14.2+/-1.2 in Nos3(+/+); P<0.01), rate of anovulation (48.3+/-7.3% in Nos3(-/-) versus 29.7+/-6.3 in Nos3(+/+); P<0.05), total mean number of recovered oocytes/zygotes (4.0+/-1.1 in Nos3(-/-) versus 10.4+/-1.6 in Nos3(+/+); P<0.01), and non-fertilization rate (50.7 in Nos3(-/-) versus 3.3% in Nos3(+/+); P<0.001). In the second trial, implantation and early pregnancy losses in Nos3-knockout and wild-type dams were detected by real-time ultrasound imaging. The number of embryos reaching implantation was higher in Nos3(+/+) than in Nos3(-/-) mice (7.5+/-0.4 vs 4.0+/-0.4; P<0.005); thereafter, embryo losses were detected between days 8.5 and 13.5, in 62.5% of the Nos3-knockout dams and, at days 10.5 and 11.5, in 16.7% of the control females (P<0.005). Thus, NO and NOS3 deficiencies affect reproductive and developmental features in the Nos3-knockout mouse model.