A New ‘Crowded Uterine Horn’ Mouse Model for Examining the Relationship Between Foetal Growth and Adult Obesity


Author for correspondence: Frederick S. vom Saal, Division of Biological Sciences, 105 Lefevre Hall, University of Missouri-Columbia, Columbia, MO 65211, USA (fax +1 573-884-5020, e-mail vomsaalf@missouri.edu).


Abstract:  Obesity is an increasing health problem, not only in developed countries but also all over the world. In addition to the focus on food intake and energy expenditure, current studies suggest two other important influences on adult body weight: birth weight and postnatal rate of growth. A common procedure in laboratory animal studies to examine the relationship of low birth weight and adult obesity is maternal nutrient restriction, but maternal undernutrition is not the basis for the majority of obese individuals in developed countries. We have thus developed a new mouse model for human obesity referred to as ‘the crowded uterine horn model’. By removing one ovary from a female CD-1 mouse, the female produces a litter of about 13 pups in one uterine horn, resulting in crowding and a 4-fold difference in placental blood flow among foetuses in a litter. Restricted placental blood flow results in intrauterine growth restriction (IUGR); these animals show a 2-fold increase in body weight during the week after weaning, while macrosomial foetuses that go through a very small amount of growth during the same postnatal period. Male mice categorized as IUGR or macrosomic at birth both are obese in adulthood. This pattern of changes in body weight throughout life in male mice mirrors findings from epidemiological studies of human foetuses with IUGR and macrosomia who become obese, and thus may provide a new model that reflects the condition of people in developed countries who become obese.