GROWTH SHANNON CLARK (F), MONICA LONGO, JOSJE LANGENVELD, G. D. V. HANKINS, GARLAND ANDERSON, GEORGE SAADE, University of Texas Medical Branch at Galveston, Obstetrics and Gynecology, Galveston, Texas, University Hospital, Maastricht, Obstetrics and Gynecology, Maastricht, Netherlands OBJECTIVE: It has been shown that an altered uterine environment affects postnatal growth. Our aim was to determine the role of cross-fostering on the altered postnatal growth in an established transgenic animal model of fetal programming induced by an abnormal uterine environment secondary to lack of endothelial nitric oxide synthase (NOS3). STUDY DESIGN: Homozygous NOS3 knockout (C57BL/6J-NOS3 / ) and wild-type mice (NOS3) were cross-bred to obtain 2 heterozygous litters that are genomically-similar but with normal (paternally-derived; NOS3 ) or abnormal (maternally-derived; NOS3 ) uterine environment. Within 24 hours of delivery, the NOS3 mat were switched to a wild-type foster mother (NOS3 ) and NOS3 pat litters to a knockout foster mother (NOS3 ). Pups from each litter were jointly counted and weighed for 21 days (weaning time), then the litters were separated by sex and weighed weekly until week 8 (adult time). The cross-fostered litters were compared with similar naturally-fostered heterozygous litters. One-way ANOVA and Newman-Keuls post hoc tests were used for statistical analysis. RESULTS: The growth curve of NOS3 pat litters was significantly higher than NOS3 , NOS3 , and NOS3 pat litters from day 13 to 21 (p ! 0.001). The growth of male NOS3 pat pups from week 4 to 8 was also significantly better compared with the other groups (p!0.05). No differences were observed between NOS3 mat and NOS3 pat litters, however these litters had significantly decreased growth at 7-8 weeks when compared to naturally-fostered NOS3 mat and NOS3 pat litters (p ! 0.05). CONCLUSION: An adverse uterine environment has a deleterious effect on postnatal growth, and its effect predominates over the postnatal environment. While an adverse postnatal environment can worsen growth, an improvement in the postnatal environment has only a slight beneficial effect. Our findings confirm the primary importance of the uterine environment and fetal programming in health and disease in later life.