Intrauterine growth retardation in endothelial nitric oxide synthase-deficient mice is established from early stages of pregnancy.
The current study aimed to determine effects of deficiencies in nitric oxide synthase (NOS) 3 on embryo and fetal development by in vivo, noninvasive, real-time ultrasonographic assessment of phenotypic changes in Nos3-knockout pregnant mice and their wild-type counterparts. From Day 4.5 of pregnancy onwards, embryonic vesicle diameters, crown-rump lengths, and trunk diameters were obtained by serial scanning of seven adult pregnant female mice, strain B6.129P2-Nos3(tm1Unc)/J, N9 generation backcrossing with C57BL/6J mice, homozygous for the disruption of the endothelial NOS gene (group Nos3(-/-)), and 12 pregnant, wild-type C57BL/6J mice (group Nos3(+/+)). All the measurements increased in both genotypes throughout gestation. However, embryo length and width were significantly larger in Nos3(+/+) than in Nos3(-/-) mice from Day 8.5, and both longitudinal and transverse diameters of the entire gestational sacs were larger in Nos3(+/+) mice from Day 10.5. Assessment of the relative growth of embryos/fetuses and gestational annexes showed different patterns among Nos3(-/-) and Nos3(+/+) mice. Throughout pregnancy, the distance between the external limit of the gestational sac and the embryo in Nos3(+/+) mice diminished in longitudinal sections, or remained unaffected in transverse sections. In Nos3(-/-) mice, there were significant increases (P < 0.005) in the differences between embryo and gestational vesicle measurements in both longitudinal and transversal curves from Days 5.5 to 14.5, but from Day 14.5 of pregnancy onward, the changes were not significant. The results demonstrate that the processes of fetal growth retardation in the Nos3(-/-) mice are established from early pregnancy stages.
Pallares
Pilar
P
Unidad de Animalario, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain. ppallares@cnic.es
Gonzalez-Bulnes
Antonio
A
D000818:Animals; D018568:Crown-Rump Length; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics; D005865:Gestational Age; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D011247:Pregnancy; D012044:Regression Analysis; D014463:Ultrasonography
D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse