Maternal Caloric Restriction prior to Pregnancy Increases the Body Weight of the Second-Generation Male Offspring and Shortens Their Longevity in Rats

Maternal undernutrition can affect offspring's physical status and various health parameters that might be transmittable across several generations. Many studies have focused on undernutrition throughout pregnancy, whereas maternal undernutrition prior to pregnancy is not sufficiently studied. The objective of our study was to explore the effects of food restriction prior to and during pregnancy on body weight and longevity of the second generation offspring. Adult female Wistar rats ("F0" generation) were 50% food restricted for one month prior to pregnancy (pre-pregnancy) or during pre-pregnancy and pregnancy. The third group was fed normally (control). The first generation offspring were normally fed until the 6th month of age to produce the second generation offspring; namely, the first-generation female rats were mated with male breeders from outside the experiment. The second generation offspring thus obtained were observed until natural death (up to 36 months). Compared to the controls, the second-generation male offspring whose "grandmothers (F0 females)" undernourished only during pre-pregnancy were significantly heavier from the 8th month of age, whereas no significant weight difference was found in the male offspring whose "grandmothers" were food-restricted during pre-pregnancy and pregnancy. Shorter lifespan was observed in the second-generation male offspring of "grandmothers" that were food-restricted either during pre-pregnancy or during pre-pregnancy and pregnancy. By contrast, no differences in body weight and lifespan were observed in all second-generation female offspring. In conclusion, maternal caloric restriction prior to pregnancy increases the body weight and shortens the longevity of the second-generation male offspring, indicating the sex-dependent transgenerational effect of maternal caloric restriction.