Abnormally high nourishment during sensitive periods results in body weight changes across generations

Objective: This study asked whether a brief period of overnutrition during a developmentally sensitive time could impact the individual's adult weight and that of succeeding generations. Research Methods and Procedures: Female rat pups (F(1) generation) were randomly assigned to 1 of 3 groups: (1) a control group that was naturally reared by mothers; (2) another control group implanted with chronic gastric fistulas on postnatal day 4 and fed enough formula to match the growth of the mother-reared group; and (3) an experimental group gastrostomized and infused from day 8 through day 16 with a greater quantity of food than gastrostomy-reared controls (OF), On postnatal day 16, both gastrostomy-reared groups were returned to normal litters. Adult F(1) females from overfed and mother-reared groups were bred with normal males to yield an F(2) generation. F(2) adult females were bred to normal males to produce an F(3) generation. Results: When adult, the F(1) experimental group was heavier than control groups. F(2) adults from OF mothers were smaller than those from the control group. F(3) animals from OF grandmothers were heavier at weaning than F(3) descendants from mother-reared animals. Discussion: Excess nourishment during a developmentally sensitive period changed the metabolic phenotype of one generation so dramatically that the gestational development and subsequent phenotype of two succeeding generations were also changed. The experiment models fetal effects of gestational diabetes in humans and may help to elucidate how, independent of genetic anomalies, secular changes can be detected across generations.