Diaz J, Taylor E M
Department of Psychology, University of Washington, Seattle 98195, USA.
Obes Res. 1998 Sep;6(5):368-74. doi: 10.1002/j.1550-8528.1998.tb00365.x.
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.
Female rat pups (F1 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 F1 females from overfed and mother-reared groups were bred with normal males to yield an F2 generation. F2 adult females were bred to normal males to produce an F3 generation.
When adult, the F1 experimental group was heavier than control groups. F2 adults from OF mothers were smaller than those from the control group. F3 animals from OF grandmothers were heavier at weaning than F3 descendants from mother-reared animals.
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.
本研究旨在探讨在发育敏感期的一段短暂营养过剩时期是否会影响个体成年后的体重以及后代的体重。
雌性幼鼠（F1代）被随机分为3组：（1）由母鼠自然哺育的对照组；（2）另一对照组在出生后第4天植入慢性胃瘘，并喂食足够的配方奶以使其生长与母鼠哺育组相当；（3）实验组在出生后第8天至第16天进行胃造口术，并输注比胃造口术饲养的对照组更多的食物（过度喂养组）。出生后第16天，两个胃造口术饲养组均放回正常的同窝幼崽中。过度喂养组和母鼠哺育组的成年F1代雌性与正常雄性交配，产生F2代。F2代成年雌性与正常雄性交配，产生F3代。
成年后，F1实验组比对照组重。过度喂养组母鼠的F2代成年鼠比对照组的小。过度喂养组祖母的F3代动物在断奶时比母鼠哺育组后代的F3代重。
在发育敏感期的营养过剩极大地改变了一代的代谢表型，以至于随后两代的孕期发育和表型也发生了变化。该实验模拟了人类妊娠期糖尿病对胎儿的影响，可能有助于阐明如何在不依赖基因异常的情况下，检测到跨代的长期变化。
