Protein malnutrition of the lactating female rat: effect on maternal behaviour and spontaneous weaning of young rats

Female rats were kept on a diet with a low content of animal protein (5.5%) beginning from the 2nd day after delivery. Beginning from the 10th day after delivery their body weight was persistently lower than that of control females. Also the body weight of their young was lower than that of control animals throughout the experiment, with significant differences appearing on the 17th day of life. Spontaneous termination of maternal milk intake occurred in malnourished young 10 days later than in the controls. Retention of 85Sr in malnourished females was in keeping with their milk production. Irrespective of the differences in body weight and the quality of solid food, the malnourished young began consuming solid food at the same age and in the same relative amounts as the controls. Thus in malnourished young the period of gradual weaning was prolonged by more than to 3 weeks in contrast to 2 weeks in the controls. This is probably due to the slower extinction of the oral sucking mechanism resulting from changes in the maturation of the CNS. No changes were found in maternal behaviour (nest building and efficiency of retrieving) in malnourished females during the suckling period. However, infanticide appeared in some females during the weaning period.     

Postnatal development and thermoregulation in the precocial European hare (<Emphasis Type="Italic">Lepus europaeus</Emphasis>)

We investigated postnatal development of captive juvenile European hares (Lepus europaeus) with respect to growth, food intake and thermoregulation. Leverets increased their body weight on average 8.5-fold within 35 days, with a peak in relative growth rate on day 8. Although leverets started to take up solid food in the 2nd week of lactation, milk was the main energy source. Leverets of larger litters (two or three young) had less energy supply via milk than those of smaller litters (one young), and digested more energy in form of solid food. Weaning weight was positively correlated with body weight at birth and decreased with increasing litter size. Metabolic rates were largely determined by ambient temperature (Ta) and the increasing body weights. Leverets were able to maintain normothermic body temperatures from the Ist day of life during cold exposure down to Ta -8 degrees C. In their 1st week of life leverets showed reduced rates of heat loss in the cold, possibly by using peripheral vasoconstriction. Our results suggest that the precocial development of leverets is characterised by high maintenance costs due to rapid growth and thermoregulation, which may lead to negative energy balances when food supply is inadequate and T(a)s are low. We hypothesise that these physiological characteristics have played an important role in the recent decline of European hare populations.     

Lactation,weaning period,food quality,and digestive tract differentiations in eutheria

Abstract Joint consideration of morphological studies, life-history data, and preferred food characteristics suggests that there may be optimal strategies for solid food supplementation during lactation for many mammals. This question was investigated by asking whether characteristics of food and morphological differentiation of the gastrointestinal tract as well as the specific differentiations of the weaning process in young eutherian mammals are related with each other and what such relationships might mean. Data on body mass, food quality, the differentiations of the digestive tract, and length of lactation and the weaning period represented the basis of the following discussion. A relatively long period when milk is supplemented by solid food is advantageous for the mother because she does not have to supply the total caloric needs of the young during lactation. On the other hand, an extended absolute length of the mixed-feeding period is advantageous for the offspring because energy is supplied by the solid food and supplemented by milk. Animals that eat high-quality food are characterized by a relatively short mixed-feeding or weaning period. In Eutheria that eat a food rich in plant cell wall material, the digestive tract shows high complexity and more than 40% of the lactation period is characterized by mixed feeding. The mother tries to reduce her energy expenditure as much as possible, while the offspring tends to obtain as much energy and building material for its developing body as possible. Both mother and young try to optimize their specific energy situation.     

Effect of growth retardation on the permeability of the blood-brain barrier in the newborn rat exposed to lead

Postnatal administration of lead to young rats via maternal milk increases the permeability of the blood-brain barrier to trypan blue. However, since this regimen delays postnatal maturation, the question arises whether growth retardation per se could explain the altered permeability to the dye. The present investigation was undertaken to examine this possibility. A first group of newborn rats were fed by dams having free access to normal food; a second group was fed by dams receiving 3% lead as the acetate salt in their food; a third group was fed by dams whose normal diet was restricted to the amount taken daily by dams of the second group. Signs of encephalopathy as shown by urinary incompetence and hind-limb paralysis were observed only in your pups exposed to lead; similarly, only the latter showed increased brain permeability to trypan blue. These results suggest that the altered permeability of the blood-brain barrier in young rats is the direct consequence of lead toxicity and not of growth retardation secondary to a nutritional effect of lead.     

Periodization of the early postnatal development in the rat with particular attention to the weaning period

The early postnatal period is characterized by a great plasticity with critical windows in which any inadequate insult or intervention may be able to influence both positively and adversely postnatal growth and development. After birth the rat littermates enter the presuckling period (initial 6 hours terminated by the first nursing), characterized by transition from the amniotic fluid to the air, by the changes of the ambient temperature, by the termination of placental nutrition and by oxidative stress. After this stage the suckling period initiates and the littermates start to consume milk of their mothers. Comsumption of milk culminates on day 15, then decreases and terminates on postnatal day 28. The end of the suckling period and the onset of physiological weaning is determined by the moment when the youngs for the first time consume the solid food together with milk (postnatal day 17 in rats). On day 19 the first intake of drinking water occurs. The weaning period terminates by the last consumption of maternal milk - on postnatal day 28. It is necessary to stress that the duration of early postnatal periods is independent of the changes of body weight. The precise knowledge of individual ontogenetic periods critical for further development is crucial for the prediction and explanation of reactions to various pathogenetic stimuli both under experimental conditions and in clinical medicine.     

Bromide transfer through mother's milk and its impact on the suckling rat

Effects of a high bromide intake in lactating rats on the performance of the dams and on the prosperity of their young were studied. In the dams, two marked consequences undoubtedly caused by high bromide intake were observed: stagnation in the extent of diet and water consumption in the course of the lactation period, and a conspicuous drop in the production rate of mother's milk. A very high intake of bromide in the mothers in the course of the nursing period (about 220 mg Br⁻/d per dam) also caused a marked decrease in the body weight increments in their suckling young. Only about one-half of these young survived and their general condition was very poor. It is suggested that one of the possible reasons for the observed marked decrease in the production of mother's milk in dams with high bromide intake could be a decreased stimulation of the mammary glands as a consequence of reduced consumption of mother's milk by the suckling. Bromide ions ingested by the dams easily moved into the rat milk. Via mother's milk, bromide was transferred in a large extent to the suckling. The amount of bromide in mother's milk depended on the bromide concentration in the drinking water taken by the dams. With the addition of 5 g bromide per liter (providing the mean daily bromide dose of 220 mg), bromide ions replaced about 54% of the chloride in the milk. A rise in the concentration of both halogens caused also an increase in the concentration of sodium in mother's milk. The exact mechanism(s) of bromide interference with postnatal developmental processes in the young remain(s) unclear. Presented in part at the, 4th International Symposium on Trace Elements in Human: New Perspectives held in Athens (Greece) on 9–11 October 2003.     

Coprophagy in young laboratory rat

Coprophagy (ingestion of maternal faeces) was found in young laboratory rats between the ages of 16 and 28 days. The degree of this activity during the given period was not constant; a multiple increase on about the 25th day was followed by an abrupt drop and complete cessation coincided with the time of spontaneous weaning. Coprophagy did not appear in prematurely weaned young (at 16 days) which were given faeces and was protracted in undernourished young whose weaning time was prolonged. Young weaned rats without having ingested maternal faeces displayed relative hyperphagy for solid food. This early hyperphagy had later consequences for the feeding behaviour of adult males, which looked for food and consumed it more intensively in a new environment and also hoarded it. Defensive behaviour was not affected.     

The formation of absorbed doses of 137Cs in the body of the female and her progeny during suckling

The transfer of 137Cs with maternal milk to progeny was studied in rats. The rats were administered with 25 kBq/g of 137Cs nitrate (pH = 6) in a single oral dose immediately after delivery. Nonpregnant females served as control. Absorbed doses per activity unit to lactating rats were 23% lover than to nonlactating ones. Over the suckling period, absorbed doses to young rats amounted to about 35% of the absorbed dose to the nursing female. For nonlactating females, the internal dose approximately equalled the sum of doses to the nursing female and young rats.     

Influence of the gastrointestinal microbiota on development of the immune system in young animals

The gastrointestinal tract (GIT) of adult mammals is colonized by a complex and dynamic community of microorganisms. Most protection against potential pathogens occurs via a mucosal immune system involving mechanisms of innate immunity as well as a secondary lymphoid organ, the gut-associated lymphoid tissue (GALT). However, the bacterial community also supports its host against invasion by potential pathogens, by a mechanism called 'colonization resistance'. Young animals need time to develop both a complex bacterial community and their immature GIT immune system, and until such developments have taken place, they are vulnerable to the presence of potential pathogens in their GIT. Initial protection against invading pathogens is provided by milk and colostrum, which contain antibodies and other bioactive components. At weaning, with the introduction of solid food and deprivation of the mother's milk, the young must also cope with a rapidly changing microbiota. The colonizing microbiota not only provides colonization resistance to potentially pathogenic bacteria. It also has a major role in the development of the intestinal immune system, both in terms of GALT development and mucosal immunity, and the induction of oral tolerance. Studies using gnotobiotic animal models have revealed that the presence of even limited numbers of the indigenous microbiota may influence the GIT immune system. Regulation of the composition of the GIT microbiota, e.g. by the use of pre- and probiotics, offers the possibility to influence the development of mucosal, and also systemic immunity.     

Biological half-lives of bromide and sodium in the rat are connected and dependent on the physiological state

The parallel course of the excretion rates of sodium and bromide ions was demonstrated in adult male rats administered simultaneously with ²⁴Na-sodium chloride and ⁸²Br-bromide. These excretion rates were inversely proportional to the magnitude of sodium intake in the animals. The biological half-life of bromide, as a substitute for sodium or chloride, was investigated with the aid of the radionuclide ⁸²Br in animals situated in very different physiological states (i.e., in lactating and nonlactating female rats as well as in young rats of varying ages [2,4,6, and 10 wk of age]). The ⁸²Br radioactivity retained in mothers and in whole litters was measured in vivo at appropriate time intervals (up to 240 h) after the application of ⁸²Br-bromide to the mothers. The time-course of the changes in the ⁸²Br radioactivity of the young was calculated as the difference between the rate of ⁸²Br intake in the mother's milk and the ⁸²Br excretion through the kidneys into the urine. The rate of ⁸²Br excretion through the kidneys of the dam could be calculated also. Nonweaned young rats (12 d) had the highest half-life (269 h) and lactating dams had the lowest (44 h). The determined values demonstrated that nonweaned young apparently conserve sodium, because of its relatively low concentration in mother's milk, whereas lactating dams, because of their large food intake, waste sodium. Presented in part at the 4th International Symposium on Trace Elements in Human: New Perspectives held in Athens (Greece) on 9–11 October 2003     

Effects of leptin administration on lactational infertility in food-restricted rats depend on milk delivery

Leptin administration has been shown to prevent the disruptive effects of acute food deprivation on reproductive function in cycling females and lactating females. We examined the ability of intracerebroventricular leptin administration to ameliorate the effects of food restriction for the first 2 wk postpartum on length of lactational infertility. Leptin administration did not reduce the effects of food restriction on reproductive function at either time period (days 8-15 and 15-22 postpartum) or dose (1 and 10 microg/day) administered. Because of the sharp contrast between these results and the ability of leptin to offset the effects of acute food deprivation in lactating rats, the remaining studies investigated the possible causes of this difference. Both central and peripheral leptin administration eliminated food deprivation-induced prolongation of lactational infertility, suggesting that neither route of administration nor dose was a factor. However, we noticed that, whereas chronically food-restricted females continue to deliver milk to their young, acutely food-deprived females do not. To test the hypothesis that the continued energetic drain of milk production and delivery might prevent the ability of exogenous leptin administration to eliminate the effects of undernutrition, leptin was administered to food-restricted, lactating rats prevented from delivering milk. In this situation intracerebroventricular leptin treatment completely eliminated the effects of food restriction on lactational infertility, suggesting that leptin contributes to the maintenance of reproductive function via two pathways: direct binding in the central nervous system and through increasing the availability of oxidizable metabolic fuels.     

Biochemical and palaeopathological investigations on weaning and infant mortality in the early Middle Ages

Weaning age of the children of the early medieval population at Wenigumstadt (Ldkr. Aschaffenburg, southern Germany, 500-700 AD) was estimated by stable nitrogen isotope analysis of bone collagen. The onset of weaning was by one year of age, when solid vegetal food subsequently replaced breast milk. In total, the change from mother's milk to solid adult food took about three years, the infants being fully weaned at this age. While the growing infant was sufficiently supported in utero and during the first months of life, the weanling's diet was insufficient for further growth and development. Starting with about 18 months of age, more and more symptoms of malnutrition are detectable on the skeletal remains, and the peak of both morbidity and mortality is reached at four years of age. Especially unspecific stress markers like Harris' lines and enamel hypoplasia clearly indicate the infants' risk of falling ill or die between three and four years of age. Malnutrition weakens the immune response, therefore the majority of inflammations detectable on the skeleton are found among the inadequately nourished children. The assumption that weaning is responsible for pathological skeletal lesions and early death in history is thus supported by archaeometry.     

The effect on growth of feeding supplemental milk or baby food to the suckling rat

Suckling rats were fed synthetic rat milk or baby food as dietary supplements amounting to 10% of their total expected daily caloric intake from day 10 to day 16 of life. On day 17, their body lipid levels were significantly higher than those of control pups, and they remained high throughout a 6-week postweaning period of ad libitum food intake. Protein content (at 17 and 60 days of age) was similar in experimental and control groups. Seventeen-day-old pups that had been fed supplemental baby food showed a small but significant increase in DNA levels but no accompanying increase in lean body mass. Rats that received supplemental milk weighed more than either those that received baby food or controls at 17 days of age; however, both experimental groups weighed considerably more at weaning (21 days) than controls. At 60 days of age, their weights were again similar to those of control rats.     

Hypothalamus integrity and appetite regulation in low birth weight rats reared artificially on a high-protein milk formula

High-protein (HP) milk formulas are routinely used in infants born with a low birth weight (LBW) to enhance growth and ensure a better verbal IQ development. Indirect evidence points to a link between an HP intake during early life and the prevalence of obesity in later life. We hypothesized that HP milk supplementation to LBW pups during early postnatal life would impact hypothalamic appetite neuronal pathways development with consequences, at adulthood, on energy homeostasis regulation. Rat pups born with a LBW were equipped with gastrostomy tubes on the fifth day of life. They received a milk formula with either normal protein (NP, 8.7 g protein/dl) or high protein content (HP; 13.0 g protein/dl) and were subsequently weaned to a standard, solid diet at postnatal day 21. Rats that had been fed HP content milk gained more weight at adulthood associated with an increase of plasma insulin, leptin and triglycerides concentrations compared to NP rats. Screening performed on hypothalamus in development from the two groups of rats identified higher gene expression for cell proliferation and neurotrophin markers in HP rats. Despite these molecular differences, appetite neuronal projections emanating from the arcuate nucleus did not differ between the groups. Concerning feeding behavior at adulthood, rats that had been fed HP or NP milk exhibited differences in the satiety period, resting postprandial duration and nocturnal meal pattern. The consequences of HP milk supplementation after LBW will be discussed in regard to neural development and metabolic anomalies.     

The dynamics of parent-offspring relationships in mammals

Evolutionary theories about parent-offspring relationships have predicted that young will aggressively demand food and care from their parents at the time of weaning - when the parents should, in their own interests, reserve their efforts for future offspring. Detailed studies of the behavioural development of mammals have given only limited support for these expectations. Often the mother is more amenable to the needs of her offspring than evolutionary theory predicts, and often offspring are sensitive to the state of their mother, tuning the pattern of their own development accordingly. Such aggression as is seen between mother and offspring tends to occur at stages other than weaning. The mismatch between theory and evidence may arise because a mother needs to monitor her offspring's state as well as her own and respond appropriately in order to maximize her own reproductive success. Similarly, an offspring needs to monitor its mother and prepare for the world in which it will grow up, in order to maximize its chances of surviving to breed.     

Physiological mechanisms,behavioral and psychological factors influencing the transfer of milk from mothers to their young

This article is part of a Special Issue “Parental Care”.Producing milk to support the growth of their young is a central element of maternal care in mammals. In spite of the facts that ecological constraints influence nursing frequency, length of time until weaning and the composition of milk, there is considerable similarity in the anatomy and physiology of milk production and delivery across mammalian species. Here we provide an overview of cross species variation in nursing patterns and milk composition as well as the mechanisms underlying mammary gland development, milk production and letdown. Not all women breastfeed their infants, thus in later sections we review studies of factors that facilitate or impede the initiation and duration of breastfeeding. The results of these investigations suggest that the decisions to initiate and maintain breastfeeding are influenced by an array of personal, social and biological factors. Finally, studies comparing the development of breastfed and formula fed infants as well as those investigating associations between breastfeeding, maternal health and mother/infant interaction are reviewed. Leading health agencies including the World Health Organization and CDC advocate breastfeeding for at least the first 6 months postpartum. To achieve these rates will require not only institutional support but also a focus on individual mother/infant dyads and their experience.     

Effect of small doses of interferon-alpha on food conditioning in young and ageing rats

Low doses (10 or 350 ME) of human interferon-alpha (HIA) were intranasally applied to young (3-4 months) and ageing (12-15 months) Wistar rats during food conditioning. In control groups, development of the conditioned reflex to acoustic stimulus (tone) did not differ significantly in young and ageing rats in the course of chronic applications of the HIA. However, the control ageing rats were better than young rats in time-interval conditioning. Small doses of HIA do not cause anorexia in rats whereas large doses do so. Tone-conditioning did not change in rats of both ages when they were treated with 10 ME of the HIA; moreover, 350 ME increased food motivation, especially in young rats. Time-interval conditioning in aging rats was descended by both doses to the level of young rats, whereas in young rats it did not change at all. We suggest that these differences between ages may by accounted for be different affinity and concentration of micro-opiod receptors (which are the targets for the HIA) in the brain structures responsible for food behaviour, and for counting time intervals.     

Consumption of milk from transgenic goats expressing human lysozyme in the mammary gland results in the modulation of intestinal microflora

Lysozyme is a key antimicrobial component of human milk that has several health-promoting functions including the development of a healthy intestinal tract. However, levels of lysozyme in the milk of dairy animals are negligible. We have generated transgenic dairy goats that express human lysozyme (HLZ) in their milk in an attempt to deliver the benefits of human milk in a continual fashion. To test the feasibility of this transgenic approach to achieve a biological impact at the level of the intestine, feeding trials were conducted in two animal models. Pasteurized milk from HLZ transgenic animals was fed to both kid goats (ruminant model) and young pigs (human model), and the numbers of total coliforms and Escherichia coli present in the small intestine were determined. Data from this proof-of-principle study demonstrate that milk from transgenic animals was capable of modulating the bacterial population of the gut in both animal models. Pigs that consumed pasteurized milk from HLZ transgenic goats had fewer numbers of coliforms and E. coli in their intestine than did those receiving milk from non-transgenic control animals. The opposite effect was seen in goats. Milk from these transgenic animals not only represent one of the first transgenic food products with the potential of benefiting human health, but are also a unique model to study the development and role of intestinal microflora on health, well-being and resistance to disease.