Pup Weight Gain Research Articles

Dietary Modulation of p-Nonylphenol–Induced Polycystic Kidneys in Male Sprague-Dawley Rats

We had previously found that p-nonylphenol (NP) at 1000-2000 ppm in a soy- and alfalfa-free diet induced severe polycystic kidney disease (PKD) in both male and female pups exposed from gestation day 7 through postnatal day (PND) 50 and hypothesized that differences in dietary components contributed to the severity of lesions relative to those reported in other studies using similar doses of NP. The present study investigated the dietary modulation of NP-induced PKD using the same exposure regimen with 2000 ppm NP in four different diets: the natural ingredient soy- and alfalfa-free diet that had been used in the earlier study, Purina 5K96; two defined diets AIN-93G, designated AIN-CAS, and a modified AIN-93G with soy protein isolate replacing casein as the protein source (AIN-SPI); and the commonly used natural ingredient diet Purina 5001 (P5001). Serum isoflavone levels were negligible in animals fed the soy-free AIN-CAS and 5K96 diets and were 2- to 18-fold higher in animals fed P5001 than in those fed AIN-SPI. Consumption of P5001 was significantly greater than consumption of the other diets, and those animals fed P5001 were generally significantly heavier than animals receiving the other diets. NP significantly reduced body weight gain in male pups regardless of the diet fed. There was no evidence of NP-induced kidney toxicity in male pups at PND 2, 14, or 21 or in the dams. In PND 50 male pups, serum blood urea nitrogen was significantly elevated by NP in all diet groups. Urine volume and urinary N-acetyl beta-glucuronidase were significantly increased by NP in the soy-free 5K96 and AIN-CAS diet groups. Relative kidney weights were increased by NP in all diet groups except P5001, with the greatest increase in AIN-CAS and 5K96 diet groups. Microscopic evaluation of kidneys from the PND 50 males showed that NP induced PKD in all diet groups but with marked variation in the severity depending on the diet. PKD was severe in 100% of the NP-treated animals in the AIN-CAS and 5K96 groups, moderate in 88% of the AIN-SPI diet group, and mild in only 40% of the P5001 diet group. Thus, diet can significantly modulate the development of PKD induced by dietary NP in rats. Soy components, as well as other complex dietary factors, may account for the level of protection afforded by the P5001 diet.

Exposure of mothers to diphenyl ditelluride during the suckling period changes behavioral tendencies in their offspring

The long-lasting possible influence of maternal exposure to 0.03 mg/kg of diphenyl ditelluride during the first 14 days of lactational period on later offspring behavior was examined in Wistar rats. Open-field locomotor activity, spontaneous alternation in the T-maze, behavior in the elevated plus-maze, motor coordination in the coat-hanger and rotorod tasks were evaluated in 30 day old pups. There were no significant specific overt signs of maternal intoxication. There were a small (less than 5%) but significant transitory differences in the body weight gain of pups between exposed and control groups, which were apparent from day 30 of suckling. Locomotor activity in the open-field task was similar between telluride and control groups. In the coat-hanger test, the latency before falling for the tellurium group was higher than that of the control group. However, the behavior of both groups was similar in the rotorod test and spontaneous alternation in the T-maze. Tellurium-treated pups presented a higher number of entries and spent more time in the open arms of the elevated plus-maze than control pups. The behavioral alterations observed here after tellurium exposure can be cautiously interpreted as an indication of behavioral disinhibition. In conclusion, this study demonstrated that dam exposure to diphenyl ditelluride can cause subtle behavioral changes in the offspring, which can be related to neurotoxic effects of diphenyl ditelluride.

Cross-fostering in coyotes: Evaluation of a potential conservation and research tool for canids

Cross-fostering has been attempted opportunistically with endangered canids as a means of increasing populations. Due to the usefulness of cross-fostering for conservation, an understanding of factors influencing success rates is essential. Using captive coyotes ( Canis latrans) as a model, we assessed the willingness of adult pairs to foster young born to other parents. We assessed the efficacy of fostering pups into existing litters (augmentation) and completely switching litters (replacement). We augmented four litters with two pups of similar age when pups were <7 days old. In addition, we replaced four entire litters when pups were <10 days old. We also augmented litters with pups 3–4 and 6–7 weeks of age. Survival, weight gain, and dominance status of pups were monitored for six weeks and compared to four control litters to determine success. All complete litter replacements were successful with survival rates among replaced pups (89.5%) similar to those of control litters (90%). For augmented litters, pup survival was dependent on the age at which fostering occurred. All pups fostered into 4 litters at <1 week of age survived beyond 6 weeks of age, two of three fostering attempts with 3–4-week-old pups succeeded, while neither of two attempts to foster 6-week-old pups succeeded. Surviving fostered pups appeared to be at no disadvantage. Weight gains were similar for pups in all treatments, and there was no evidence of reduced dominance status among fostered pups as compared to natal pups in the same litters. These results illustrate that genetic relatedness is not essential for successful fostering and does not appear to alter dominance patterns; however the age at which pups are fostered may affect the success of fostering attempts.

A study of the role of neuro-glial remodeling in the oxytocin system at lactation

Under conditions of strong secretion of neurohypophysial hormone, such as during parturition, lactation and dehydration, the hypothalamic oxytocin-system displays a remarkable morphological plasticity such that astrocytic coverage of its neurones diminishes, their surfaces become directly juxtaposed and contacted by an increased number of synapses. A growing body of evidence indicates that these anatomical changes have an impact on glutamatergic neurotransmission in the supraoptic nucleus, and may be therefore of physiological consequence. We here evaluated the consequences of the inhibition of such plasticity on the overall activity of the oxytocin system during lactation. Remodeling was prevented by performing hypothalamic microinjections in gestating rats of endoneuraminidase, an enzyme that removes polysialic acid from the neural cell adhesion molecule. Our earlier studies established that the presence of polysialic acid is a prerequisite for remodeling of the oxytocin system in the supraoptic and paraventricular nuclei. In dams in which polysialic acid was absent in all magnocellular nuclei after bilateral endoneuraminidase injections, parturition was normal and neither the frequency nor the amplitude of suckling-induced reflex milk ejections was different from vehicle-treated dams. The weight gain of pups was also normal as was water intake by the dams. We then assessed the electrical activity of antidromically identified magnocellular neurones in the polysialic acid-free supraoptic nucleus of isoflurane-anesthetized lactating rats. Basal and bursting activity characteristic of oxytocin neurones before each reflex milk ejection was not significantly different from that recorded in the supraoptic nucleus of rats with normal levels of polysialic acid. Our results indicate that neuro-glial remodeling, despite its role on fine modulation of oxytocin neuronal activity, is not essential to parturition and lactation.

Complex‐environment rearing prevents prenatal hypoxia‐induced deficitsin hippocampal cellular mechanisms necessary for memory consolidationin the adult Wistar rat

Hypoxic episodes in utero can result in enduring and debilitating neurological sequelae that include nonprogressive motor disorders and/or significant learning deficits. The extent of long-term disruption of synaptic function following prenatal hypoxia and its subsequent effect on learning ability, however, remain to be established. Polysialylation of the neural cell adhesion molecule, a cellular event integral to the consolidation of diverse learning paradigms, was used to correlate cellular end points with learning deficits as a consequence of prenatal hypoxia. Pregnant Wistar dams exposed to hypobaric hypoxia during gestational days 10-20 had significantly reduced litter sizes, but the lack of effect on subsequent pup weight gain suggested no gross developmental deficit. By contrast, adult animals with prior in utero hypoxia exhibited significant learning difficulties in both acquisition of a water maze spatial learning task and recall of a passive avoidance paradigm. Learning deficits correlated with a significant reduction in the frequency of polysialylated neurons in the dentate infragranular zone and a blunting of their transient activation 12 hr following task acquisition. Rearing animals with prior prenatal hypoxia in a complex environment, however, eliminated the task acquisition and recall deficits and restored dentate polysialylated cell frequency and their transient posttraining increase.

Neonatal mortality from in utero exposure to perfluorooctanesulfonate (PFOS) in Sprague–Dawley rats: Dose–response, and biochemical and pharamacokinetic parameters

Perfluorooctanesulfonate (PFOS) is a widely distributed, environmentally persistent acid found at low levels in human, wildlife, and environmental media samples. Neonatal mortality has been observed following PFOS exposure in a two-generation reproduction study in rats and after dosing pregnant rats and mice during gestation. Objectives of the current study were to better define the dose–response curve for neonatal mortality in rat pups born to PFOS-exposed dams and to investigate biochemical and pharmacokinetic parameters potentially related to the etiology of effects observed in neonatal rat pups. In the current study, additional doses of 0.8, 1.0, 1.2, and 2.0 mg/kg/day were included with original doses used in the two-generation study of 0.4 and 1.6 mg/kg/day in order to obtain data in the critical range of the dose–response curve. Biochemical parameters investigated in dams and litters included: (1) serum lipids, glucose, mevalonic acid, and thyroid hormones; (2) milk cholesterol; and (3) liver lipids. Pharmacokinetic parameters investigated included the interrelationship of administered oral dose of PFOS to maternal body burden of PFOS and the transfer of maternal body burden to the fetus in utero and pup during lactation, as these factors may affect neonatal toxicity. Dosing of dams occurred for 6 weeks prior to mating with untreated breeder males, through confirmed mating, gestation, and day four of lactation. Dose levels for the dose–response and etiological investigation were 0.0, 0.4, 0.8, 1.0, 1.2, 1.6, and 2.0 mg/kg/day PFOS. Statistically significant decreases in gestation length were observed in the 0.8 mg/kg and higher dose groups. Decreases in viability through lactation day 5 were observed in the 0.8 mg/kg and higher dose groups, becoming statistically significant in the 1.6 and 2.0 mg/kg dose groups. Reduced neonatal survival did not appear to be the result of reductions in lipids, glucose utilization, or thyroid hormones. The endpoints of gestation length and decreased viability were positively correlated, suggesting that late-stage fetal development may be affected in pups exposed to PFOS in utero and may contribute to the observed mortality. Benchmark dose (BMD) estimates for decreased gestation length, birth weight, pup weight on lactation day 5, pup weight gain through lactation day 5, and viability resulted in values ranging from 0.27 to 0.89 mg/kg/day for the lower 95% confidence limit of the BMD 5 (BMDL 5). Results of analyses for PFOS in biological matrices indicate a linear proportionality of mean serum PFOS concentration to maternal administered dose prior to mating and through the first two trimesters of gestation. However, at 21 days of gestation, mean serum PFOS concentrations were notably reduced from values measured earlier in gestation. Urinary and fecal elimination was low as expected from prior observations in adult rats. Significant transfer of PFOS from dam to fetus in utero was confirmed, and results suggest that dam and corresponding fetal body burdens, as indicated by serum and liver PFOS levels, correlate with neonatal survival.

Differential Growth of Own and Alien Pups in Mixed Litters of Mice: A Role for Genomic Imprinting?

AbstractFemale mice are said to be unable to distinguish own from alien offspring and will indiscriminately nurse each other's young in communal nests. Here, we present results of a split‐litter experiment that tested whether offspring growth was affected depending on whether they were nursed by their own or unrelated foster mothers. Pups of reciprocal crosses between C57/B6 and CBA/Ca strains were fostered in mixed litters that consisted half of their natural siblings and half of unrelated littermates of the reciprocal genotype. Analysing the relative growth of the two pup types showed that offspring gained proportionally more weight when nursed by their own mothers than their cross‐fostered litter mates during the period from day 15 until weaning, during which maternal provisioning effort contributes to pup weight gain. Before day 15 of the pups’ life, however, we found no advantage of being nursed by biological mothers, and we suggest that this may be due to the effects of paternally expressed genes in young that mask their maternal identity, thus favouring indiscriminate nursing of all young in a communal nest.

Adverse Effects of Prenatal Exposure to Atrazine During a Critical Period of Mammary Gland Growth

Prenatal exposure to 100 mg/kg atrazine (ATR) delays mammary gland (MG) development in resulting female offspring of Long-Evans rats. To determine if the fetal MG was sensitive to ATR effects during specific periods of development, timed-pregnant dams (n = 8/group/block) were dosed for 3- or 7-gestation day (GD) intervals (GD 13-15, 15-17, 17-19, or 13-19) with 100 mg ATR/kg/day or vehicle (C), and their offspring were evaluated for changes. Mammary glands taken from pups prenatally exposed to ATR displayed significant delays in epithelial development as early as postnatal day (PND) 4 compared to C, with continued developmental delays at later time points that varied by time of exposure. However, the most persistent and severe delays were seen in the GD 17-19 and GD 13-19 ATR exposure groups, demonstrating statistically similar growth retardation. Because MG developmental deficits persisted into adulthood, we hypothesized that ATR-exposed animals may have had difficulties nursing their young. Females exposed prenatally to either ATR (as defined) or C (n = 4 litters/group) were bred, and the resulting F(2) offspring from GD 17-19 and GD 13-19 exposure groups were significantly smaller in body weight (BW) than C. In a separate study, it was determined that ATR (25-100 mg/kg), delivered from GD 15-19, did not decrease fetal body weights on GD 20, even though the higher doses significantly decreased weight gain of the dosed dams. These data suggest that the consequences of brief ATR exposure during a critical period of fetal MG development (GD 17-19), are both delayed MG development of the offspring and inadequate nutritional support of F2 offspring, resulting in adverse effects on pup weight gain.

Growth and hepatic in vitro metabolism of ergotamine in mice divergently selected for response to endophyte toxicity

This study investigated if genetic differences exhibited in endophyte-resistant and -susceptible mouse lines had persisted after 13 generations in which the integrity of lines was maintained yet selection ceased. Experimental groups were mouse lines fed an endophyte-free (E−) or -infected (E+) diet. The in vitro metabolism of the ergot alkaloid ergotamine in mouse liver microsomes was characterized by LC-MS/MS and compared between both lines before and after exposure to E+ feed. No difference in the average daily weight gain of pups between resistant and susceptible mice was observed on the E+ diet. Thus, for the weight gain selection criterion under study, the difference established between the two lines appears not to have persisted over the extended period of relaxed selection. Microsomal incubations produced nine predominate peaks in the HPLC assay. The peaks were confirmed by LC-MS/MS to be ergotamine, ergotamine epimer, monohydroxylated metabolites (M1, M2, M1e, M2e) and dihydroxylated metabolites (M3–5). A gender difference for metabolite formation was observed on the E− diet, in that females produced a greater amount of M1, M1e and M3–5 than males. When challenged with the E+ diet, mice showed differences in concentration of M3 for line (resistant > susceptible) and gender (female > male) and of M4 and M5 for gender (female > male). Gender differences in the metabolism of ergotamine have not been shown before in these lines of mice or other species used to study ergot alkaloid metabolism. This adds a potential source of variation in the susceptibility to fescue toxicity not explored previously and would be of value to investigate further.

Effect of aqueous extract of Acacia nilotica ssp adansonii on milk production and prolactin release in the rat.

In view of the traditional belief that Acacia nilotica ssp adansonii (AN) can stimulate milk production in lactating women, experiments were performed to determine the effect of an aqueous extract of AN on milk production in rats. Female rats that received oral doses of aqueous extract of this plant during their first lactation produced about 59% more milk than controls (P<0.01). Pup weight gain was also significantly higher than that in the control group. A lower dose, comparable to that used by women to improve their milk yield, led to about 33% more milk with the same growth rate for pups as that in the high-dose group. The extract of AN was found to stimulate the synthesis and release of prolactin (PRL) significantly (P<0.05). In addition, the mammary glands of oestrogen-primed rats treated with the extract showed clear lobuloalveolar development with milk secretion. This study demonstrates that the aqueous extract of AN can stimulate milk production and PRL release in the female rat and could consequently have the properties claimed for lactating women.

Central blockade of oxytocin receptors during late gestation disrupts systemic release of oxytocin during suckling in rats.

There is evidence that the central oxytocin system is activated and undergoes reorganization before parturition. The present study was designed to determine the effects of central oxytocin receptor blockade during late gestation on parturition, pup growth, and oxytocin release during suckling. Female Sprague-Dawley rats were implanted on gestation day 12-14 with Alzet osmotic minipumps containing an oxytocin receptor antagonist (d(CH2)5, Tyr(Me)(2), Orn(8)-vasotocin; OT-X) or artificial cerebrospinal fluid (VEH), which was infused into the third cerebral ventricle. Pumps were removed within 24 h of parturition. Daily maternal body weight and food intake were monitored during gestation and lactation. The length of gestation, duration of parturition, pup number, litter weight and interbirth interval were recorded. Subsequently, pup number and litter weights were recorded daily until lactation day 10 or 11, when maternal and pup behaviour, and plasma oxytocin concentration before and during suckling were measured. Central oxytocin blockade had no effect on the timing of parturition, maternal behaviour, litter size, still births, or litter weights at birth. However, beginning on day 3 of lactation, average weights of litters of OT-X females were significantly lower than litters of VEH-treated females. Furthermore, while basal plasma oxytocin concentrations, oxytocin increases in response to suckling and dam/pup interactions did not differ between groups, a significant delay in suckling-induced systemic oxytocin release was observed in OT-X females. Finally, OT-X dams weighed less than VEH dams during the postpartum observation period, although food intakes were similar. These data suggest that central actions of oxytocin during late gestation are necessary for the normal timing of systemic release of oxytocin during suckling, normal pup weight gain, and maintenance of maternal body weight.

Factors affecting pup growth and survival in co‐operatively breeding meerkats Suricata suricatta

Summary We examined the relative importance of maternal, environmental and social factors for post‐weaning pup growth and survival in a co‐operatively breeding mammal, the meerkat Suricata suricatta . Pup daily weight gain was primarily influenced by the number of carers per pup and the daily weight gain of those carers. Rainfall and daily temperatures had additional positive and negative effects, respectively, on weight gain of pups born to subordinates. Pup overnight weight loss was primarily influenced by the amount of weight pups gained during the day, and their age. However, pups also lost considerably more weight overnight when temperatures were cold, although such effects were less in large groups. Pup growth rates were positively influenced by the number of carers per pup and carer condition, and negatively influenced by high daytime temperatures. Pup weight at independence was positively associated with weight at emergence and pup weight gain during provisioning, but negatively associated with the extent of overnight weight loss. Pup survival between emergence and independence was related to maternal status, pup sex and overnight weight loss, as well as to group size, daytime temperature and monthly rainfall. Thus, in meerkats, social factors largely, but not wholly, replace the importance of maternal factors that are commonly found to govern reproductive success in non‐co‐operatively breeding social vertebrates.

Behavioural and morphometric measurements of parental investment in southern elephant seals at the Falkland Islands

Parental investment is a key variable in the study of breeding strategies and life-histories evolution. In Pinnipedia, parental investment is usually calculated from direct measurements of pup weight gain or energy transfer between the mother and the pup. These direct methods always involve handling and restraining procedures that pose practical, logistical and ethical problems. To evaluate if weighing can be substituted by indirect observational estimates of parental investment, we analysed the relationship among various behavioural measures of suckling and post-natal growth in the southern elephant seal population of Sea Lion Island (Falkland Islands). Behavioural measures were in all cases a poor predictor of true investment as estimated by weighing. We concluded that there are currently no effective alternatives to direct handling, and that the best way to reduce the potential adverse impact of investment studies is the improvement of the handling protocol, which should include an estimation of the long-term effects on the health of handled animals. Further research is needed to test the validity of non-behavioural indirect methods (e.g. 3D photogrammetry).

Evaluation of spinosad in a two-generation dietary reproduction study using Sprague-Dawley rats.

Spinosad, an insecticide derived from a naturally occurring bacterium via fermentation, represents a new class of insecticides acting by a novel mode of action. A dietary study was conducted in Sprague-Dawley rats in which groups of 30 rats/sex/dosage level were given diets that provided 0, 3, 10, or 100 mg spinosad/kg body weight/day, 7 days/week, for 2 successive generations. Following 10 weeks of dietary exposure, the P1 generation was mated twice to produce F1a and F1b litters. After weaning, groups of 30 rats/sex/dosage level were selected from the F1a litters, given diets containing spinosad for 12 weeks, and mated to produce the F2 generation. Dietary administration of spinosad to rats at a dosage of 100 mg/kg/day over 2 generations produced parental toxicity and effects on the offspring. Among adult males, body weights and weight gains were decreased 2-9% relative to controls, with P1 males more affected than P2. Absolute and relative liver, kidney, heart, spleen, and thyroid weights were increased by from 12% to as much as 240% of control values. Histologic changes consistent with cationic amphiphilic compounds were noted in the kidneys, lungs, mesenteric lymph nodes, spleen, and thyroid of P1 and P2 males and females. In females given 100 mg/kg/day, though premating body weights were not affected, weight gains during the F1a and F1b gestation periods were depressed 15-16%. Increased incidences of dystocia, and vaginal bleeding and mortality occurred during parturition and lactation at 100 mg/kg/day. Effects on the offspring (decreased litter size and survival through day 4 of lactation) were limited to the high-dosage group. Signs indicative of poor maternal care noted in the pups (stomachs void of milk, cold, thin, etc.) were observed at 100 mg/kg/day. Early postnatal effects on the offspring were considered likely secondary to the effects in maternal animals around the time of parturition. At 100 mg/kg/day, weight gain in pups was depressed throughout lactation, with statistically significantly decreased weights noted toward the latter half of the lactation period. There were no treatment-related effects on adults or their offspring at 3 or 10 mg/kg/day in either generation. Based on these results, spinosad is not considered a selective reproductive toxicant, (i.e., no effects on reproductive parameters were noted below a level that produced toxicity in the adults) and the no observed effect level (NOEL) for both parental and reproductive/perinatal toxicity was 10 mg/kg/day.

Effects of Controlled Compensatory Growth on Mammary Gland Development and Lactation in Rats

The objective of this study was to examine the effect of compensatory growth nutritional regimen on mammary gland growth and lactation. One hundred twenty-two Sprague Dawley female rats (35 days of age) were randomly assigned to either a control or a stair-step compensatory nutrition (SSCN) feeding regimen or an alternating 2-2-3-3-week schedule beginning with 40% energy restriction for 2 weeks followed by re-alimentation (control diet) for 2 weeks. Pup weight gain and milk yield were improved 8% and 8 to 15%, respectively, by the SSCN regimen. The gene expression of β-casein was 2.3-fold greater in the SSCN group than in the control group during early lactation, but they were greater at all stages of the second lactation. The gene expression of insulin-like growth factor-1 was 40% lower in the SSCN group than in the control group during early lactation of the second lactation, but during late lactation it was 80% greater than in the control group. The concentration of serum corticosterone tended to be higher in the SSCN group during the late stage of the first lactation. These results suggest that the stair-step compensatory nutrition regimen improves lactation performance and persistency by modulation of cell differentiation and apoptotic cell death.

Effects of helpers on juvenile development and survival in meerkats.

Although breeding success is known to increase with group size in several cooperative mammals, the mechanisms underlying these relationships are uncertain. We show that in wild groups of cooperative meerkats, Suricata suricatta, reductions in the ratio of helpers to pups depress the daily weight gain and growth of pups and the daily weight gain of helpers. Increases in the daily weight gain of pups are associated with heavier weights at independence and at 1 year of age, as well as with improved foraging success as juveniles and higher survival rates through the first year of life. These results suggest that the effects of helpers on the fitness of pups extend beyond weaning and that helpers may gain direct as well as indirect benefits by feeding pups.

Effects of bromantan on offspring maturation and development of reflexes

Bromantan ( N-[2-adamantil]- N-[ para-bromphenyl]amine) is an “actoprotective” drug widely used in Russia as a muscle performance-enhancing agent for sportsmen and as an immunostimulator in medicine. Experiments were conducted to determine whether this compound has adverse effects on the reproduction and development of offspring. Sexually mature female rats, weighing 180–200 g, were orally given bromantan at doses of 30 mg/kg (30-mg/kg group), 150 mg/kg (150-mg/kg group) and 600 mg/kg (600-mg/kg group) daily for 16 days, while the controls received the vehicle, amylaceous solution. Afterwards, treated females were mated with untreated males. The body weight change of the pregnant rats was monitored, as well as the length of gestation, litter size, sex ratio and number of stillborn. The offsprings were weighed and observed for external malformations, abnormalities of conditioned and unconditioned reflexes and open-field behaviour. Observation of rat dams revealed that their general state and activity in all groups did not differ significantly both during and after bromantan treatment. Bromantan had no adverse effects on body weight and gestation length of dams. Number of dams delivered per group did not differ from controls. There were stillborn rat pups in all litters, but the control group had less. One dam in the first group delivered a rat pup with a head hematoma. Litter size of the 30- and 600-mg/kg groups was decreased (by 34.9% and 44.2%, respectively) and increased in the 150-mg/kg group (by 45.1%, P<.05) in comparison with controls. Bromantan had insignificant different effects on the sex ratio of newborn in all treatment groups. Survival of pups over the first 3 months showed a loss of 40% for the 150-mg/kg group and 20% for controls. During the remaining time, death rate did not exceed 3–6% and did not differ from those of the controls. Pups in the 30- and 600-mg/kg groups showed significantly higher weight gain during the first week (7th PND) of observation by 83.69% and 58.02%, respectively, compared to controls; subsequently, this difference in the 600-mg/kg group decreased rapidly to insignificant levels, but the 30-mg/kg group remained significantly different until PND 35 and then again at PND 77–112. Dynamics of body weight gain of rat pups in the 150-mg/kg group during the whole (but not on PND 7) period of observation was insignificantly (on PNDs 14, 42 and 49 significantly) lower than that of the control group. Study of the functional state of rat pups' nervous system at different stages of postnatal development revealed insignificant differences in the expression of reflexes compared with those of the control group. Negative geotaxis was completed by the 8th day in controls and in treated groups earlier by an average of 1–2 days. Surface righting was completed by the controls on the 8th day, in the 30-mg/kg group on the 6th day and in other treated groups on the 7th day. Cliff avoidance appeared a day ahead for rat pups in treated groups compared with controls. Air righting reflex in the 30- and 600-mg/kg groups was observed a day earlier than in the controls. Significant differences were observed only for two parameters (negative geotaxis and surface righting); in both cases, rat pups of the 30-mg/kg group differed from the control and 150-mg/kg groups. Early development of physical parameters was also noted, but significant differences from the control group were obtained only in the 30-mg/kg group for incisor eruption. While all pups demonstrated strength of fore and hind limbs by postnatal day 16, treated pups increased their times of maintaining their grasp (PND 15). Open-field testing (PND 40) resulted in an insignificant decrease of exploratory and locomotor behaviors for the 30-, 150- and 600-mg/kg groups. The number of grooming episodes was insignificantly decreased for the 30-mg/kg group and insignificantly increased for the 600-mg/kg group. In the passive avoidance testing, on the retention day (72 h later), entry latency for rat pups in the 30-, 150- and 600-mg/kg groups increased by 259.0%, 175.3% and 160.7%, respectively ( P<.05), over their training day, while in the control group, time increased only by 1.8%.

Growth performance and reproductive traits at first parity of New Zealand white female rabbits as affected by heat stress and its alleviation under Egyptian conditions.

Exposing growing and adult New Zealand White (NZW) female rabbits to severe heat stress (temperature-humidity index = 28.9) during summer adversely affected their growth and reproductive traits. The traits that declined significantly (p < 0.01) were the live body weight, daily weight gain and feed intake of growing rabbits, and the litter size and litter weight at weaning (p < 0.05) and the pre-weaning weight gain of pups (p < 0.01) for adult females. The conception rate declined considerably with heat stress. The declines in the values of the digestibility coefficients due to heat stress were 7.9% (p < 0.05) for dry matter (DM), 8.1% (p < 0.05) for crude protein (CP) and 1.0% for crude fibre (CF). The traits that increased significantly (p < 0.01) due to heat stress were water intake, water/feed ratio and rectal temperature in growing rabbits and pre-weaning mortality for adult females. Alleviation of heat stress in the growing and adult female NZW rabbits was more efficient with drinking cool water (10-15 degrees C; between 10:00 and 17:00) than with supplementation with palm oil (as a source of energy) or natural clay (as a natural enhancer to growth and milk production). Supplying the animals with cool drinking water gave the highest body weight and weight gain, conception rate, litter size and weight and digestibility coefficients for DM and CP and the lowest rectal temperature, respiration rate and pre-weaning mortality. The loss in rabbit production pertaining to heat stress estimated from the percentages of decline in conception rate x pre-weaning mortality x litter weight at weaning was 73.0%. The provision of cool water restored 11/12 of heat loss.

Prenatal heroin exposure: Effects on development, acoustic startle response, and locomotion in weanling rats

The purpose of this study was to investigate the effects of prenatal heroin exposure on the offspring in postnatal behavioral development. Pregnant Sprague-Dawley rats were injected daily (s.c.) with 10mg/kg of heroin from gestational day 8 to 20. The control dam received saline injections and the pair-fed dam received saline and was yoked to a weight-matched heroin-treated dam. Litters were culled to eight to ten pups and weighed at postnatal day (PND) 1, 8, 15, and 22. Acoustic prepulse inhibition and habituation were parameters used for evaluating the sensorimotor gating and simple form of learning respectively. Locomotor activity and rearing were assessed using the photobeam activity system. All behavioral tests were performed on the offspring at PND 21 to 23. Results showed that heroin treatment significantly reduced maternal food intake, water consumption, and weight gain. Both heroin-exposed and pair-fed groups showed a marked reduction in birth weight in both male and female pups when compared with controls; however the postnatal weight gain in heroin-exposed pups was significantly lower than the pair-fed group by 3 weeks postnatally, particularly in the female pups. These female pups also showed a significant increase in ambulation and rearing when compared to the pair-fed pups. The habituation rate in both types of behavioral tests was also decreased in these female pups as compared to control and pair-fed groups. The present study indicated that prenatal heroin exposure could result in a marked retardation of postnatal development and learning. These effects are sex related.

Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,000 ppm and 75,000 ppm. An additional high-dose group received 75,000 ppm ARA-oil in combination with 55,000 ppm fish oil containing docosahexaenoic acid (DHA), at a ratio of ARA to DHA, comparable to the ratio in mother's milk of 2:1. The total levels of fat in each diet were kept constant by adding the appropriate amounts of corn oil. A concurrent control group received 130,000 ppm corn oil in the diet. An additional carrier control group was fed unsupplemented rodent diet. Administration of the test substances from 4 weeks prior to mating, throughout mating, gestation, lactation of parental (F 0) animals and weaning of the F 1 pups did not affect fertility or reproductive performance, nor the general condition of pups, viability, sex ratio or number of pups. Pup weight gain in the ARA/DHA-oil group was lower than the controls administered equal amounts of corn oil. In the subsequent subchronic study survival, clinical signs, body weight gain and food consumption were not adversely affected by the test substances. Ophthalmoscopic examination did not reveal any treatment-related changes. There were no treatment-related effects observed up to dietary test substance concentrations of 15,000 ppm. The following statistically significant differences were found in the ARA high-dose group and /or in the ARA/DHA group compared to the corn oil control group: decreased alkaline phosphatase activity, decreases in cholesterol, triglycerides and phospholipids concentrations, increased creatinine and urea concentrations. Furthermore, these groups showed increased adrenal, spleen and liver weights. The incidence of hepatocellular vacuolation was increased in females of the ARA high-dose group and the ARA/DHA group. Oil droplets were observed in the mesenteric lymph nodes and in the intestinal villi in the ARA high-dose group and the ARA/DHA group. In addition, lipogranulomas were observed in the mesenteric lymph nodes in these groups. The observed changes in the high-dose groups may be effects of the high intake of high-fat levels, rather than specific effects of the ARA-oil. The no-observed-effect level in this study was placed at 15,000 ppm ARA-oil. This level is equivalent to approximately 970 mg ARA-oil/kg body weight/day.