Effects of prenatal and postnatal exposure to vitamin A on the development of the murine immune system

Vitamin A and its derivatives are known to enhance the immune system and affect embryogenesis. In this study, five daily subcutaneous injections of retinol palmitate (0.001 mg/kg body weight) were administered to eight female SW mice before mating. Six more weekly injections of retinol palmitate were given during pregnancy and lactation. Eight controls were similarly treated with saline. Four of the eight vitamin-A-treated females had litters, whereas seven of the eight saline-treated females had litters. Resultant litters did not differ in size or appearance. At 12 weeks of age, serum IgM and IgG1 levels were significantly higher in the progeny of vitamin-A-treated mothers before but not after immunization with a test antigen, sheep red blood cells (SRBC). This difference was not seen when other progeny were tested at the age of one year. Anti-SRBC titers did not differ in the two groups of progeny at the age of 12 weeks or one year. One-year-old progeny of vitamin-A-treated mothers weighed significantly more than did control progeny; significant enlargement of the heart, spleen, and kidneys was observed. However, organ-to-body-weight ratios did not differ significantly. In a separate experiment, adult female mice treated with varying doses of vitamin A (five daily doses of 0.0001, 0.0005, or 0.001 mg/kg body weight) showed a dose-dependent reduction of serum IgG1 and hematocrits, but no change in serum IgM levels or leukocyte counts. Resting untreated mice had IgM levels which were one-half those seen in saline-treated controls. These studies indicate that large doses of vitamin A can affect some aspects of the developing and mature murine immune system.     

The outcome of acute schistosomiasis infection in adult mice with postnatal exposure to maternal malnutrition

Maternal malnutrition during the lactation period in early development may have long-term programming effects on adult offspring. We evaluated the combined effects of parasitological behaviour and histopathological features and malnutrition during lactation. Lactating mice and their pups were divided into a control group (fed a normal diet of 23% protein), a protein-restricted group (PR) (fed a diet containing 8% protein) and a caloric-restricted group (CR) (fed according to the PR group intake). At the age of 60 days, the offspring were infected with Schistosoma mansoni cercariae and killed at nine weeks post-infection. Food intake, body and liver masses, leptinaemia, corticosteronaemia, collagen morphometry and neogenesis and the cellular composition of liver granulomas were studied. PR offspring showed reduced weight gain and hypophagia, whereas CR offspring became overweight and developed hyperphagia. The pre-patent period was longer (45 days) in both programmed offspring as compared to controls (40 days). The PR-infected group had higher faecal and intestinal egg output and increased liver damage. The CR-infected group showed a lower number of liver granulomas, increased collagen neogenesis and a higher frequency of binucleate hepatocytes, suggesting a better modulation of the inflammatory response and increased liver regeneration. Taken together, our findings suggest that neonatal malnutrition of offspring during lactation affects the outcome of schistosomiasis in mice.     

Increased anxiety-like behavior during the post-stress period in mice exposed to repeated restraint stress

Mice exposed to repeated restraint (RR: 2 h of restraint on each of 3 consecutive days) lose weight and do not return to the weight of non-stressed controls after restraint ends. These mice also exhibit an exaggerated endocrine response to mild stressors in the post-stress period. To determine if other aspects of the stress response are altered, NIH Swiss mice were repeatedly restrained then evaluated for anxiety-like behavior in various behavioral tests. Twelve days after the end of RR half of the control and RR mice were subjected to the mild stress of an intraperitoneal injection of saline before placement in an elevated plus maze. RR mice not subjected to mild stress showed the same level of anxiety as the control and RR mice exposed to mild stress. Placement in a light-dark box 20 days after restraint also indicated an increase in anxiety-like behavior in RR mice that had not been exposed to mild stress. In contrast, RR mice displayed no increase in anxiety-like behavior in the defensive withdrawal apparatus and the marble burying test 6 and 17 days, respectively, after restraint. RR mice released more corticosterone than non-restrained controls exposed to defensive withdrawal or EPM apparatus although baseline corticosterone remained at control levels. These results suggest that RR induces an exaggeration of both endocrine and behavioral responses to subsequent mild stressors. This post-stress hypersensitivity to mild stress may contribute to the sustained reduction in the body weight of RR animals.     

Effects of repeated blood samplings on locomotor activity, evasion and wheel-running activity in mice

The effects of serial blood sampling on nocturnal locomotor activity, evasion, wheel-running activity and body mass were studied in male NMRI mice aged 7-8 weeks. The erythrocyte count, haematocrit and haemoglobin concentration at the beginning and end of the study showed no difference in group 1 (two samples per week, 0.08 ml each) while there was a significant decrease in the group 2 values (three samples per week, 0.08 ml each). The total amount of nocturnal locomotor activity decreased in the animals bled repeatedly while the periods with locomotor activity increased. These alterations appeared particularly after bleeding. In the test-group animals evasion showed a decrease compared with the untreated control animals, but there was no evidence of a relation to the timing of the bleedings.     

Effects of isoflurane exposure during pregnancy on postnatal memory and learning in offspring rats

Emerging evidence has demonstrated that exposure to anesthetics early in life caused neurohistopathologic changes and persistent behavioral impairments. In this study, a maternal fetal rat model was developed to study the effects of isoflurane exposure during pregnancy on postnatal memory and learning in the offspring. Pregnant rats at gestational day 14 were either exposed to 1.3% isoflurane in a humidified 100% oxygen carrier gas or simply humidified 100% oxygen without any inhalational anesthetic for 2 h every day before delivery. Four weeks later, spatial learning and memory of the offspring were examined using the Morris Water Maze. The expression levels of GAP-43 and NPY in the hippocampal CA1 region of the pups were determined by immunohistochemistry and RT-PCR. Simultaneously, the ultrastructure changes in synapse of the hippocampus were also observed by transmission electron microscopy (TEM). Isoflurane exposure during pregnancy impaired postnatal spatial memory and learning in the offspring as shown by the longer escape latency and the fewer original platform crossings in the Morris Water Maze test. The number and optical densities of GAP-43 and NPY positive cells, as well as the levels of GAP-43 and NPY mRNA, decreased significantly in the hippocampus of isoflurane-exposed pups. Furthermore, TEM studies showed remarkable changes in synaptic ultrastructure of hippocampus. These results indicate that isoflurane exposure during pregnancy could cause postnatal spatial memory and learning impairments in offspring rats, which may be partially explained by the down-regulation of GAP-43 and NPY in the hippocampal area.     

Detrimental effects of tobacco smoke exposure during development on postnatal lung function and asthma

Exposure to environmental tobacco smoke (ETS) during fetal development and early postnatal life is perhaps the most ubiquitous and hazardous of children's environmental exposures. The developing lung is highly susceptible to ETS. A large body of literature links both prenatal maternal smoking and children's ETS exposure to decreased lung growth. This review summarizes the state of the knowledge, including both human epidemiology and laboratory animal experiments, linking ETS, lung development, and respiratory outcomes. Important issues discussed include lung development and lung function and asthma in relation to ETS exposure during critical windows of growth. Prenatal exposure to ETS is associated with impaired lung function and increased risk of developing asthma, whereas postnatal exposure mainly acts to trigger respiratory symptoms and asthma attacks, but it also plays an important role in the occurrence of asthma in children. This review provides evidence that avoidance of ETS exposure both before and after birth is beneficial to long-term respiratory health, because airway function in later life is believed to be largely determined by lung development occurring in utero and in early infancy.     

Thymidine kinase activity in cardiac muscle during embryonic and postnatal development

Cytoplasmic thymidine kinase from cardiac muscle of the rat has been characterized. It has a pH optimum of 9.0 and a K(m) value for thymidine of 1.6mum. The sedimentation coefficient of this enzyme in sucrose gradients is 4.5S, which represents a molecular weight of approx. 69000. Thymidine kinase prepared from cardiac muscle of foetal, neonatal and adult rats is inhibited by dTTP and dTDP; there is neither inhibition nor stimulation by dTMP, dCTP, dATP, dGTP or cyclic AMP. The activity of thymidine kinase in differentiating cardiac muscle of foetal and neonatal rats declines progressively with development, reaching adult values of almost zero by the fifteenth to seventeenth day of postnatal development. This represents a 70-fold decrease in enzyme activity from 3 days before birth to 17 days after birth. The loss of thymidine kinase activity in differentiating cardiac muscle correlates temporally with the cessation of DNA biosynthesis and the loss of cytoplasmic DNA polymerase activity in this tissue.     

Adenylate cyclase activity in rat submandibular gland during postnatal development

Adenylate cyclase activity was measured in homogenates of submandibular glands of 1 to 42 day old rats. During this period of time the gland reached its final stage of differentiation. Adenylate cyclase activity was higher in the glands of one day old rats than in those of 7 and 14 day old animals. Between 14 and 28 days of age the enzyme activity more than doubled and approached the level that characterized the glands of adult animals. Fluoride (10mM) stimulated the enzyme activity in all age groups but the stimulation was less in the case of one day old rats as compared to older animals. Isoproterenol (10^?4 M) stimulated adenylate cyclase by 50–60% in the gland of adult rats but had no effect on the enzyme activity in 7 to 28 day old animals. Administration of isoproterenol for 5 days to 9 day old rats increased the weight of the submandibular gland by 70 per cent. Total adenylate cyclase activity increased parallel with the weight of the gland but the specific activity of the enzyme remained unchanged. It is concluded that during the postnatal development of the submandibular gland the rapid increase in adenylate cyclase activity occurs after weaning and it coincides with an accelerated rate of functional differentiation of the acinar cells.     

Effect of exposure to high isoflavone-containing diets on prenatal and postnatal offspring mice

Isoflavone (IF), a type of phytoestrogen, has multiple beneficial effects, but too much phytoestrogen can have adverse effects on offspring. To examine whether chronic exposure to high IF has adverse effects on reproductive development, mice offspring were exposed to IF through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning until sacrifice. In male offspring, there was no difference between the IF group and controls; however, in female offspring in the IF group, remarkably earlier puberty and induction of multioocyte follicles on postnatal day (PND) 21 were observed. Gene expression levels of estrogen receptor beta decreased in the ovary and vagina on PND 21. These results suggest that chronic exposure to higher than normal levels of IF induces alterations in the reproductive development of female mice through an estrogenic effect.     

Effects of single or repeated dermal exposure to methyl parathion on behavior and blood cholinesterase activity in rats

The effects of a single or repeated dermal administration of methyl parathion on motor function, learning and memory were investigated in adult female rats and correlated with blood cholinesterase activity. Exposure to a single dose of 50 mg/kg methyl parathion (75% of the dermal LD(50)) resulted in an 88% inhibition of blood cholinesterase activity and was associated with severe acute toxicity. Spontaneous locomotor activity and neuromuscular coordination were also depressed. Rats treated with a lower dose of methyl parathion, i.e. 6.25 or 12.5 mg/kg, displayed minimal signs of acute toxicity. Blood cholinesterase activity and motor function, however, were depressed initially but recovered fully within 1-3 weeks. There were no delayed effects of a single dose of methyl parathion on learning acquisition or memory as assessed by a step-down inhibitory avoidance learning task. Repeated treatment with 1 mg/kg/day methyl parathion resulted in a 50% inhibition of blood cholinesterase activity. A decrease in locomotor activity and impairment of memory were also observed after 28 days of repeated treatment. Thus, a single dermal exposure of rats to doses of methyl parathion which are lower than those that elicit acute toxicity can cause decrements in both cholinesterase activity and motor function which are reversible. In contrast, repeated low-dose dermal treatment results in a sustained inhibition of cholinesterase activity and impairment of both motor function and memory.     

Changes in homologous recombination frequency in Arabidopsis thaliana plants exposed to stress depend on time of exposure during development and on duration of stress exposure

In the past, we showed that exposure to abiotic and biotic stresses changes the homologous recombination frequency (HRF) in somatic tissue and in the progeny. In current work we planned to answer the following question: do stress intensity/duration and time during exposure influence changes in somatic HRF and transgenerational changes in HRF? Here, we tested the effects of exposure to UV-C, cold and heat on HRF at 7, 14, 21 and 28 days post germination (dpg). We found that exposure at 14 and 21 dpg resulted in a higher increase in HRF as compared to exposure at 7 dpg; longer exposure to UV-C resulted in a higher frequency of HR, whereas prolonged exposure to cold or heat, especially at later developmental stages, had almost no effect on somatic HRF. Exposure at 7 dpg had a positive effect on somatic growth of plants; plants exposed to stress at this age had larger leaves. The analysis of HRF in the progeny showed that the progeny of plants exposed to stress at 7 dpg had an increase in somatic HRF and showed larger sizes of recombination spots on leaves. The progeny of plants exposed to UV-C at 7 dpg and the progeny of plants exposed to cold or heat at 28 dpg had larger leaves as compared to control plants. To summarize, our experiments showed that changes in somatic and transgenerational HRF depend on the type of stress plants are exposed to, time of exposure during development and the duration of exposure.

Electronic supplementary material

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