Effect of prenatal hypoxia during organogenesis on albino rat behavior during postnatal period

The survival rate, physical development, and spontaneous behavior has been evaluated in pups of albino rats exposed to acute hypobaric hypoxia on the 9–10th day of gestation corresponding to the onset of organogenesis. Prenatal hypoxia increased the mortality among the offspring, delayed their physical development, and affected their spontaneous behavior up to the age of 2 months. The females exposed to intrauterine hypoxia proved to be more sensitive to hypoxia than males.     

Acute antenatal hypoxia on different stages of embryogenesis changes the offspring behavior patterns and biogenic amine levels

The effects of acute hypobaric hypoxia on the stages of progestation or beginning of organogenesis on biogenic amines levels in brain stem and cerebral cortex of their mature offspring as well as on their behavior, were investigated. It was shown that acute hypoxia applied in the period of embryonic organogenesis resulted in severe delayed changes in offspring spontaneous behavior and led to marked changes of biogenic amine levels, particularly expressed for dopaminergic system. Females subjected to antenatal hypoxia happened to be more sensitive to its influences than males.     

Comparative analysis of ECG characteristics in pregnant rats subjected to acute hypoxia in the period of organogenesis

Various ECG characteristics are investigated in white rats subjected to acute hypobaric hypoxia on the 9th–10th day of gestation corresponding to the period of organogenesis. The hypoxia-induced changes in the ECG characteristics are different in groups with a low, middle, and high resistance to acute hypoxia.     

The effect of low-level prenatal X-irradiation on postnatal development in the Wistar rat

The objective of this investigation was to determine the effect of low-dose prenatal X-irradiation on postnatal growth and neurobehavioral development, and whether alterations would manifest at dosages lower than those which produce anatomic malformations from exposure at the most sensitive period of organogenesis. Ninety-eight Wistar strain rats were exposed to 0.1, 0.2, or 0.4 Gy X-radiation of were sham irradiated on the 9th or 17th day of gestation. A conventional teratologic evaluation was completed on half of the animals (572 fetuses). The age of appearance of four physiologic markers and of acquisition of six reflexes was observed in 372 offspring. Exposure during early organogenesis at these levels had no effect on any of these parameters. Prenatal exposure to X-radiation on the 17th day of gestation at dosage levels greater than 0.1 Gy resulted in alterations in the appearance of three postnatal neurophysiologic parameters. Growth retardation throughout the postpartum period also was observed in the offspring. The induction of developmental and reflex alterations had a comparable threshold to the known threshold for anatomic malformations on the 9th day. These results indicate that all of the parameters studied had thresholds either at or above 0.2 Gy acute radiation, and that the postpartum developmental and reflex acquisition measures were not more sensitive indicators of exposure to X-radiation than growth parameters.     

Prenatal Entrainment of Rat Testicular Malate Dehydrogenase Activity Circadian Rhythm

In mammals the photoperiodic synchronization of circadian system starts before birth. During fetal and neonatal period mothers relay the photoperiodic information to their litter. The maternal pineal melatonin 24 h cycle acts as a synchronizing signal. We have studied the effect of pineal maternal sympathetic denervation and administration of melatonin to mothers denervated during gestation on the prenatal synchronization of testicular malate dehydrogenase (MDH) activity circadian rhythm of the offspring 25 days after birth. When mothers were denervated at the 7th, 10th or 11th day of gestation, pups showed disruption of testicular MDH activity circadian rhythms. In contrast, no disruptive effect was observed when the mothers were denervated on the 12th or 14th day of gestation. When denervated mothers (7th day of gestation) were treated with a daily dose of melatonin from the 11th to the 14th day of gestation, pups showed a MDH activity circadian rhythm. The hormone failed to impose a daily phase when administered from the 9th to the 12th day of gestation. Results suggest that prenatal synchronization in the rat occurs very early in the development, before suprachiasmatic nuclei morphologic arrangement and functional activity begin.     

Prenatal Entrainment of Rat Testicular Malate Dehydrogenase Activity Circadian Rhythm

In mammals the photoperiodic synchronization of circadian system starts before birth. During fetal and neonatal period mothers relay the photoperiodic information to their litter. The maternal pineal melatonin 24 h cycle acts as a synchronizing signal. We have studied the effect of pineal maternal sympathetic denervation and administration of melatonin to mothers denervated during gestation on the prenatal synchronization of testicular malate dehydrogenase (MDH) activity circadian rhythm of the offspring 25 days after birth. When mothers were denervated at the 7th, 10th or 11th day of gestation, pups showed disruption of testicular MDH activity circadian rhythms. In contrast, no disruptive effect was observed when the mothers were denervated on the 12th or 14th day of gestation. When denervated mothers (7th day of gestation) were treated with a daily dose of melatonin from the 11th to the 14th day of gestation, pups showed a MDH activity circadian rhythm. The hormone failed to impose a daily phase when administered from the 9th to the 12th day of gestation. Results suggest that prenatal synchronization in the rat occurs very early in the development, before suprachiasmatic nuclei morphologic arrangement and functional activity begin.     

Influence of intermittent normobaric hypoxia during early organogenesis on the development of white rats

The influence of antenatal intermittent normobaric hypoxia during early organogenesis (days 9–10 of intrauterine development) on the physical development, vegetative balance, and antioxidant defense system of 60-day-old rats was studied. Antenatal exposure to intermittent hypoxia resulted in the impaired physical development of all offspring during the early 15-day postnatal period and caused changes in the vegetative balance of heart regulation, which were differently directed in males and females. Moreover, females that survived antenatal hypoxia had a decreased superoxide dismutase activity in the brain, compared to that in the control rats.     

Effect of prenatal exposure to diagnostic ultrasound on the development of mice.

Pregnant Swiss albino mice were exposed to diagnostic ultrasound (3.5 MHz, approximately 65 mW) for 10 min on Day 3.5 (preimplantation period), 6.5 (early organogenesis period), or 11.5 (late organogenesis period) of gestation. Sham-exposed controls were maintained for comparison. Exposed as well as control fetuses were dissected out on the 18th day of gestation, and changes in total mortality, body weight, body length, head length, brain weight, sex ratio, and microphthalmia were recorded. Exposure on Day 3.5 of gestation resulted in a small increase in the resorption rate and a significant reduction in fetal body weight. A low fetal weight and an increase in the number of growth-retarded fetuses were produced by exposure on Day 6.5 postcoitus. A statistically nonsignificant increase in the incidence of microphthalmia was induced in fetuses exposed on Day 6.5 or Day 11.5 of gestation. These results indicate that ultrasound may have some adverse effects on the mouse embryos depending on the developmental stage at which the exposure occurred.     

Effect of hypoxia in early perinatal ontogenesis on behavior and structural characteristics of the rat brain

The study has shown that acute hypoxia in newborn rat pups can lead to disturbances in processes of formation of brain structures, behavior reactions, and learning in the subsequent ontogenesis. The single normobaric hypoxia at the 2nd day of life causes retardation of such integrative parameter or general development and growth as body mass at the period of feeding. In such animals, essential disturbances of the sensorimotor development were revealed in forms of delay of reflex reactions of turning on a plane, negative geotaxis, and avoidance of edge. Also detected was action of hypoxia on hanging on a rope by using front legs (a symptom of muscle weakness). Morphological study has shown all studied functional zones of neocortex (motor, sensomotor, auditory, visual) to response stereotypically to the early postnatal action of hypoxia. The death of nerve cells is predominant in the II–III associative layers, the sizes and number of pyramidal neurons are sharply decreased. Different hippocampus fields maturing after death in mammals show a characteristic response to hypoxia. In individual hippocampus fields there was detected a different degree of death of neurons, with predominance in the CA3 and CA4 fields. A possibility of modeling the perinatal encephalopathy with minimal brain dysfunctions in children is discussed.     

The effect of gamma irradiation on the structure and enzymatic activity of the nuclear membrane of the liver in pregnant rats and their embryos]

Morphological and biochemical investigations of pregnant rats and embryo liver cell nuclei after in vivo irradiation in the doses of 1 and 2 Gr revealed their high radiosensitivity at all stages of gestation and embryonal development. At damaging effect of radiation, we managed to observe sharp accumulation of products of lipid peroxide oxidation and suppression of the activities of such enzymes as cytochrome-c-oxidase, NAD.N-cytochrome-c-reductase, ATPase and RNAase in liver nuclei of pregnant rats and embryos. The changes of such a kind are shown to intensify with the increasing of irradiation doses. The most profound inhibition of the activities of these enzymes in liver nuclei of embryos irradiated in utero was observed during the period of organogenesis (the 13th day of the development) and in fetal period of embryogenesis (the 17th day of the development), as well as at the 13th and 17th day of gestation. The morphological data also demonstrate the high level of cell nucleus sensitivity to the action of radiation during gestation and embryogenesis.     

Conditional Reflex Reaction of the Passive Avoidance in Female and Male Rats Exposed to Hypoxia at Different Terms of Prenatal Development

Elaboration of the conditional reflex reaction of passive avoidance was studied in the 42–46-day old offsprings of two groups of female rats: intact (control) and exposed to action of hypoxia at the 13th, 16th or 19th day of pregnancy. The parameter of learning was the time of stay of the rats in a dark camera, in which they obtained an electroshock. It is shown that the prenatal hypoxia has different effect on the ability to elaborate the conditional reflex reaction of passive avoidance in female and male rats. By this parameter, no differences were revealed in the male group between the control and the animals exposed to hypoxia at different terms of intrauterine development. In female exposed to hypoxia at the 19th day of gestation, it was not possible to elaborate the conditional reflex reaction of passive avoidance. In females exposed to hypoxia at the 13th day of gestation the parameters of learning were lower, whereas in the females exposed to hypoxia at the 16th gestation day they were higher than in control animals.     

Teratogenic action of Rifaximin in the rat and rabbit and its effect on perinatal development in the rat

The purpose of this study is to evaluate the teratogenic action and the effect on perinatal development of Rifaximin. Teratogenic action of Rifaximin was studied in the rat and in the rabbit. The drug was administered by gavage during organogenesis period at 50 and 100 mg/kg; idroxyurea and thalidomide were used as teratogenic drugs. The effect on physical and behavioural development of the pups was studied in the rat at 50 and 100 mg/kg during the foetal period and suckling time. The search for malformation of internal organs was carried out on the half of the fetuses fixed according to Wilson; the examination of the skeleton of the other fetuses was carried out according to Dawson. Some parameters of physical and behavioural development were evaluated in the pups. Rifaximin at these dosages has no teratogenic effects and does not influence the psychophysical development of the pups.     

Transgenerational consequences of acute antenatal stress in pregnant rats

The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed.     

Threshold levels of maternal nicotine impairing protective responses of newborn rats to intermittent hypoxia.

Experiments were carried out to determine the threshold level of maternal nicotine that impairs protective responses of rat pups to hypoxia. From days 6 or 7 of gestation, pregnant rats received either vehicle or nicotine (1.50, 3.00, or 6.00 mg of nicotine tartrate. kg body wt(-1).day(-1)) or vehicle continuously via a subcutaneous osmotic minipump. On postnatal days 5 or 6, pups were exposed to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2) or 3% CO(2)) and their time to last gasp was determined, or they were exposed to intermittent hypoxia and their ability to autoresuscitate from hypoxic-induced primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp or the total number of gasps when the pups were exposed to a single period of hypoxia. The number of successful autoresuscitations on repeated exposure to hypoxia was, however, decreased in pups whose dams had received either 3.00 or 6.00 mg of nicotine tartrate/kg body wt; these dosage regimens produced maternal serum nicotine concentrations of 19 +/- 6 and 35 +/- 8 ng/ml, respectively. Thus our experiments define the threshold level of maternal nicotine that significantly impairs protective responses of 5- to 6-day-old rat pups to intermittent hypoxia such as may occur in human infants during episodes of prolonged sleep apnea or positional asphyxia.     

Disturbances in Formation of the New and Old Cortex at Changes of Conditions of Embryonic Development

Using a model of acute hypoxia during pregnancy of rats, changes in the development of old (hippocampus) and new (sensorimotor) cortex associated with disturbance of neuronogenesis have been revealed in the studied brain structures at the period of action of a pathological factor. It was found that in rats submitted to hypoxia at the 13–14th days of embryogenesis, the number of degenerating neurons (including the pyramidal ones) at various levels of chromatolysis increased since the 5th day after birth; the increase was present for the entire first month of postnatal development. In the cortex of rat pups submitted to prenatal hypoxia there were observed deformation of neuronal bodies, vacuoles in the cytoplasm, shrinkage of apical dendrites of pyramidal neurons and delayed development of the structure (time of the appearance of spikes, formation of structural elements and the size of the cells) of the nervous tissue of the brain of the rat pups exposed to prenatal hypoxia. The columnar structure of the cortex was disturbed. In hippocampus, the process of degeneration of neurons started by 2–3 days later than in the cortex; by two weeks of postnatal development a massive degeneration and death of a part of neurons were also revealed. The morphometrical analysis showed a decrease in the number of neurons and their total area in the sensorimotor cortex (the layer V) and an increase in the number of glial elements at the 10–17th days after birth. In the hippocampus a decrease in the area occupied by neurons and in their size was detected in adult animals. The adult rats submitted to prenatal hypoxia were found to have disturbances of memory and learning. A correlation was shown between the disturbances of the conditions of embryonic development and the changes in the ability of learning and storage of new skills in the offspring.     

Postnatal behavioral consequences of antenatal intermittent hypoxia experienced during early organogenesis in mature rats

This study analyses the spontaneous behavior and anxiety-phobic status of mature rats that were subjected to antenatal intermittent hypoxia during the early stages of organogenesis. Antenatal intermittent hypoxia caused a decrease of motor activity as well as an enhanced anxiety level in rats of both sexes, while males appeared to be more sensitive to hypoxic influence. The effects of single antenatal intermittent hypoxia were more expressed than those of double exposure.     

Prenatal epoxiconazole exposure effects on rat postnatal development

Although some studies have pointed out to embryo/fetal toxicity, knowledge about the potential toxicity of the fungicide epoxiconazole is still limited. Once the results of these previous studies have raised some concern, this study studied the effects of epoxiconazole maternal exposure on the physical endpoints in the development of rat pups. To accomplish that, the effects of epoxiconazole (50.0, 100.0, and 150.0 mg/kg) were examined when rats were exposed at two different developmental stages: during the first 6 days of pregnancy or in the organogenesis period (6-15 days). After parturition, pups were tested for growth and maturational milestones. Maternal exposure to the fungicide, independently of phase, resulted in significantly early mean time to vaginal opening and delayed time to testes descent in pups. Weight gain rate in pups and their mothers was not affected for the tested exposure period. The findings of this study emphasize that epoxiconazole maternal exposure may lead to alterations in developmental patterns in nursing pups, consistent with the known influence of epoxiconazole on steroid hormone synthesis.     

Effects of litter size on maternal care, body weight and infant development in golden hamsters (Mesocricetus auratus)

The effects of litter size on maternal care, body weight and infant development of golden hamsters were investigated from a longitudinal perspective. Litters were culled to 1,3,6 and 9 pups, and the behavior and body weight of mothers and pups were recorded from the 5th to the 25th postpartum day. We noted that the time spent by mothers in bodily interactions with pups decreased as a function of litter size; maternal pup retrievals reached their maximum around the 13-15th day, which coincided with the increased locomotor activity of pups at this time; the total number of pup retrievals by the mother increased as a function of the litter size, but mothers of larger litters were more 'efficient' (i.e. they failed less frequently in exhibiting a full sequence of retrievals) and exhibited a low litter-size proportional mean number of retrievals. All mothers gradually lost body mass throughout lactation, and decrease in body weight was significantly related to litter size. The mean body weight gain (%) by pups decreased as a function of litter size, but we also noted that single and larger litter pups exhibited a decreased body mass (grams) by the 15th day, suggesting that infant development may be impaired at both extremes of experimental conditions. We concluded that the behavior of mothers and pups was affected by the litter size, and it appeared that the litter had an optimal size-not so large as to overlap the mother's physical capacity, and not so small as to fail to compensate for the parental investment.     

Developmental and neurobehavioural toxicity study of arsenic on rats following gestational exposure

To characterize developmental and behavioral alterations induced by arsenic exposure, Albino rats were exposed to arsenic (0, 1.5, 3.0 and 4.5 mg/kg/day/po) from gestation day 8 to till parturition and the offspring were observed over the first 3 postnatal weeks, until they were weaned on post-natal day (PND) 21. Once the pups were delivered (PND0), the treatment was discontinued. All pups were assessed for physical development, reflex development, strength and motor coordination from standard neurobehavioural developmental test batteries beginning on PND1. Gestational administration of arsenic at tested dose levels, showed no significant changes in the day of appearance of eye opening, startle reflex, negative geotaxis and spontaneous alteration performance in comparison to the control group. The number of live fetuses, mean fetal body weight and percentages of resorptions or malformations per litter were not affected by arsenic exposure. No treatment-related malformations or developmental variations were noted at any exposure level, suggesting that arsenic exposure at this dose level did not adversely affect behavioural endpoints of developmental toxicity.     

Development of hamster circadian rhythms: Role of the maternal suprachiasmatic nucleus

Summary During development, the circadian rhythms of rodents become entrained to rhythmicity of the mother. Rhythms in behavior and in neuroendocrine function are regulated by a circadian pacemaker thought to be located within the suprachiasmatic nucleus (SCN) of the hypothalamus. Evidence indicates that this pacemaker begins to function and to be entrained by maternal rhythms before birth. Although the maternal rhythms which mediate prenatal entrainment of the fetal circadian pacemaker have not been identified, it is likely that they are regulated by the maternal SCN.The role of the maternal SCN in entrainment of the offspring was examined in Syrian hamsters (Mesocricetus auratus) by measuring the activity/rest rhythms of pups. Using the synchrony among the rhythms of pups within a litter as an indication that the pups had been entrained, the effect on entrainment of ablating the maternal SCN was determined. Lesions of the maternal SCN which were performed early in gestation (day 7) and which destroyed at least 75% of the SCN were found to disrupt the normal within litter synchrony among pups, indicating interference with the normal mechanism of entrainment.The effect of lesions on day 7 of gestation could mean that the maternal SCN is important for entrainment of the pups before birth, after birth, or during both of these times. To determine if the maternal SCN is specifically important for prenatal entrainment, lesions were performed two days before birth on day 14 of gestation. Lesions of the maternal SCN on day 14 were not as disruptive as were lesions on day 7. This suggests that the maternal SCN is important between days 7 and 14 of gestation and that the synchrony normally observed at weaning is already established, in part, on or before day 14 of gestation. This further suggests that an entrainable circadian pacemaker is present in the fetus only two weeks after fertilization.Abbreviations SCN suprachiasmatic nucleus - L:D light:dark - LL constant light - r mean vector length - 2DG 2-deoxyglucose - NAT N-acetyltransferase