Maternal overnutrition before and during pregnancy induces DNA damage in male offspring: A rabbit model.

Using a rabbit model, we investigated whether maternal intake of a high-fat and high-carbohydrate diet (HFCD) before and during pregnancy induces an increase in micronuclei frequency and oxidative stress in offspring during adulthood. Female rabbits received a standard diet (SD) or HFCD for two months before mating and during gestation. The offspring from both groups were nursed by foster mothers fed SD until postnatal day 35. After weaning, all the animals received SD until postnatal day 440. At postnatal day 370, the frequency of micronuclei in peripheral blood reticulocytes (MN-RETs) increased in the male offspring from HFCD-fed mothers compared with the male offspring from SD-fed mothers. Additionally, fasting serum glucose increased in the offspring from HFCD-fed mothers compared with the offspring from SD-fed mothers. At postnatal day 440, the offspring rabbits were challenged with HFCD or continued with SD for 30 days. There was an increase in MN-RET frequency in the male rabbits from HFCD-fed mothers, independent of the type of challenging diet consumed during adulthood. The challenge induced changes in serum cholesterol, LDL and HDL that were influenced by the maternal diet and offspring sex. We measured malondialdehyde in the liver of rabbits as an oxidative stress marker after diet challenge. Oxidative stress in the liver only increased in the female offspring from HFCD-fed mothers who were also challenged with this same diet. The data indicate that maternal overnutrition before and during pregnancy is able to promote different effects depending on the sex of the animals, with chromosomal instability in male offspring and oxidative stress and hypercholesterolemia in female offspring. Our data might be important in the understanding of chronic diseases that develop in adulthood due to in utero exposure to maternal diet.

Determining the period, phase and anticipatory component of activity and temperature patterns in newborn rabbits that were maintained under a daily nursing schedule and fasting conditions.

During the last decade, lagomorphs have gained relevance as valuable models for the study of the development of circadian rhythmicity. This relevance is due to both the peculiar behavior of the lactating doe, in which maternal care is limited from 3 to 5 min per day, and the temporal organization that newborn rabbits exhibit during the early stages of development. In this study, we characterized the development of the temporal pattern of core body temperature and locomotor activity of newborn rabbits. This activity was recorded simultaneously for individual newborn rabbits and was maintained under constant light conditions, a 24-h nursing schedule and without access to the lactating doe. In addition, different mathematical algorithms were designed to determine the period, phase and anticipatory component of the time series obtained for the newborn rabbits. During the first two weeks of life, the average gross locomotor activity decreased as age increased; conversely however, the core body temperature exhibited a significant increment during the early stages of postnatal development. The newborn rabbits' circadian patterns of activity and temperature were consolidated as early as the first week of life. Similarly, the acrophase and nadir of both rhythms were settled by postnatal day 5, and the maximum activity consistently occurred approximately 2 h before the animals' maximum body temperature. The anticipation of nursing was evident from postnatal day 2 for both parameters, and the duration and intensity showed changes associated with the stage of development. In addition, the anticipatory component persisted with the same duration and intensity, even when nursing was omitted. The mathematical methods used in this study are suitable for producing unbiased analyses of the time series that are obtained from developing animals in situations during which biological signals generally show variability in frequencies and trends. By using these methods, it was possible to establish that circadian rhythmicity at the behavioral and physiological levels was evident during the first week of age in newborn rabbits. This circadian rhythmicity represents an endogenous rhythm because it persists throughout constant conditions.