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

Abstract

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 6 th 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 8 th 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.

Gender differences in developmental programming of cardiovascular diseases

“…Global nutrient restriction in one generation also resulted in transgenerational effect with BP increased in male offspring of the F2 and F3 generations despite the absence of additional insult during their gestational period [88]. The effect of exposure to maternal undernutrition in the F1 also impaired vascular function in the F1 offspring and subsequent generations [88] Nutrient restriction initiated prior to pregnancy also reduced life expectancy in the second-generation male offspring [89]. Thus, these studies suggested that fetal exposure to nutrient restriction in one generation not only increased CV risk in the F1 generation, but also transmitted that risk to the next generations of male offspring.…”

Non-genomic transmission of longevity between generations: potential mechanisms and evidence across species

“…Thus far, only one study provides direct evidence that rodent longevity can be transmitted across generations. In this study, dietary restriction during preconceptional or both preconceptional and gestational periods resulted in increased body weight and life shortening in the second-generation male, but not the female offspring [ 69 ].…”

Epigenetic inheritance of proteostasis and ageing

“…In fact, several studies in rats show that offspring born to mothers fed on a low-protein diet during pregnancy have shorter lifespans [ 47 – 49 ] and become less fertile at a younger age [ 49 – 51 ] than those fed on a normal diet. Moreover, recent studies suggest that maternal nutrient restriction may also result in reduced F2 offspring lifespan [ 52 ] and accelerated reproductive ageing [ 53 ]. This accelerated ageing and loss of fertility may be linked to increased oxidative stress [ 51 , 54 ], which is known to contribute to ageing.…”