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This Article Full Text Full Text (PDF) All Versions of this Article: 78/6/1002    most recent biolreprod.107.066159v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pallares, P. Articles by Gonzalez-Bulnes, A. PubMed PubMed Citation Articles by Pallares, P. Articles by Gonzalez-Bulnes, A. Agricola Articles by Pallares, P. Articles by Gonzalez-Bulnes, A.

Intrauterine Growth Retardation in Endothelial Nitric Oxide Synthase-Deficient Mice Is Established from Early Stages of Pregnancy¹

Unidad de Animalario,³ Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain Departamento Reproduccion Animal,⁴ Instituto Nacional de Investigación y Tecnologia Agraria y Alimentaria, 28040 Madrid, Spain

ABSTRACT

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.

conceptus, early development, knockout mice, nitric oxide, pregnancy

¹Supported by Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Instituto Nacional de Investigación y Tecnologia Agraria y Alimentaria (INIA), under the collaborative project CC07-018. CNIC is supported by the Spanish Ministry of Health and Consumer Affairs and the Pro-CNIC Foundation; INIA is supported by the Spanish Ministry of Education and Science Affairs; there was no other outside funding.

Correspondence: ²Pilar Pallares, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernandez Almagro 3, 28029 Madrid, Spain. FAX: 34 91 453 12 65; e-mail: ppallares{at}cnic.es