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Effects of maternal and pre-weaning undernutrition in rat offspring: Age at reproductive senescence and intergenerational pup growth and viability
Citation:
CHERNOFF, N., M. I. GAGE, T. E. STOKER, R. L. COOPER, M. E. GILBERT, AND E. H. ROGERS. Effects of maternal and pre-weaning undernutrition in rat offspring: Age at reproductive senescence and intergenerational pup growth and viability. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 28(4):489-494, (2009).
Impact/Purpose:
Maternal and/or postnatal undernutrition are widespread in human populations and are components of many experimental developmental and reproductive toxicology bio-assays. This study investigated in utero and/or pre-weaning undernutrition effects on reproductive maturation and senescence in the CD rat as well as potential intergenerational effects. Pregnant rats (F0 generation) were given food ad libitum or at 50% of normal dietary intake. Their offspring (control or intrauterine growth retarded (IUGR)) (F1 generation) were cross-fostered as 8 or 16-pup litters (control and undernourished) and reproductive parameters studied in these animals. The data are potentially important to the EPA in two ways: The first concerns human health implications since inadequate maternal nutrition is present in all Nations including our own. Body weights of IUGR pups were, as expected, reduced. The prenatal environment had little effects on the onset of male reproductive maturity, but it was delayed in animals experiencing early postnatal undernutrition in the large litters. Similar body weight effects were observed in females but there was no difference in the age of vaginal opening. A potentially important finding was made in terms of the onset of reproductive senescence in females. The senescence as measured by onset of estrus acyclicity occurred at a younger age in IUGR-8 pup and Control-16 pup groups compared to Control-8 or IUGR-16 pup groups. This follows a similar pattern noted with respect to pre- and postnatal influences on high blood pressure and Type II diabetes in human populations. It has been shown that higher incidences of these adverse health effects occur in populations experiencing IUGR followed by optimal postnatal diets. The effects are not found to same degree in populations experiencing optimal pre- and postnatal food access or populations experiencing IUGR and subsequent sub-optimal food access – it is the population that has different nutritional states pre- and postnatally that is most at risk. Whether these effects are applicable to humans will obviously require epidemiological studies. F1 females from all groups were bred to F1 control males and no evidence of adverse reproductive effects was found in any F2 groups. This indicates that the rat is not a good model for the intergenerational reproductive effects in humans reported in a number of epidemiology studies. The second potential impact involves laboratory studies investigating lifetime exposure to environmental agents. In utero exposures often involve maternal undernutrition due to general toxicity and subsequent fetal and neonatal growth retardation. Unless scientists know what the effects of simple undernutrition are, lifetime data obtained on groups of animals exposed both to agents of concern will be impossible to confidently ascribe to agent-induced toxicity if early undernutrition is present as a confounder. This study yield important baseline data for pure undernutrition that may be used to differentiate between agent-induced adverse effects and those due to secondary maternal toxicity.
Description:
Maternal and/or postnatal undernutrition are widespread in human populations and are components of many experimental developmental and reproductive toxicology bio-assays. This study investigated in utero and/or pre-weaning undernutrition effects on reproductive maturation and senescence in the CD rat as well as potential intergenerational effects. Pregnant rats were given food ad libitum or at 50% of normal dietary intake. Their offspring (control or IUGR) were cross-fostered in 8 or 16-pup litters (control and undernourished). Body weights were reduced and onset of male reproductive maturity delayed in animals from large postnatal litters. Similar body weight effects were observed in females but there was no difference in the age of vaginal opening. Female reproductive senescence as measured by onset of estrus acyclicity occurred at a younger age in IUGR-8 pup and Control-16 pup groups compared to Control-8 or IUGR-16 pup groups. Females were bred to control males and no evidence of adverse reproductive effects was found in any F2 groups.
