Gestational and lactational transfer of melamine following gavage administration of a single dose to rats

Melamine contamination in an infant formula manufactured by a firm in China was reported in September 2008. Maternal transfer of melamine during pregnancy and through breast-feeding are possible ways of introduction. This study aims to evaluate the maternal transfer of melamine into amniotic fluid and breast milk through oral intake by pregnant and lactating rats, respectively. The quantity of melamine in the dam’s sera, amniotic fluid, breast milk as well as in fetal whole body extract was measured. Our results showed that, after administration of single dose of 21.4 mg/kg per body weight of melamine to pregnant rats (16-18 days of gestation) by gavage, about 80% of melamine was found in dam’s serum in 0.5 h. Melamine further reached the fetuses through placental transfer as it was found that peak melamine level of 7.15 ppm (∼30%) was detected in the fetuses after 2 h and 4.36 ppm (∼20%) was shown in amniotic fluid after 3 h of maternal intake. In the lactating rats, about 40% of maternal intake of melamine was transferred to breast milk and peaked at 3 h. The results of this study confirmed the maternal transfer of melamine to fetuses in utero and infants through breast feeding.     

Physiological regulation in cigarette exposed infants: an examination of potential moderators

The primary purpose of this study was to examine pathways from prenatal cigarette exposure to physiological regulation at 2 months of age. Specifically, we explored the possibility that any association between prenatal cigarette exposure and infant physiological regulation was moderated by fetal growth, prenatal or postnatal environmental tobacco smoke (ETS) exposure or maternal depressive symptomatology during pregnancy. We evaluated whether exposed infants who were also exposed to ETS after birth, were small for gestational age (SGA) or had mothers with higher depressive symptoms during pregnancy had the highest levels of physiological dysregulation. Respiratory sinus arrhythmia (RSA) was obtained from 234 (166 exposed and 68 nonexposed) infants during sleep. As expected, cigarette-exposed infants had significantly lower RSA than nonexposed infants. This association was not moderated by prenatal or postnatal ETS exposure, or maternal depressive symptomatology during pregnancy. However, small for gestational age status did moderate this association such that nonexposed infants who were not small for gestational age had a significantly higher RSA than nonexposed small for gestational age infants and exposed infants. These findings provide additional evidence that prenatal cigarette exposure is directly associated with dysregulation during infancy.     

Maternal exposure to Δ9-tetrahydrocannabinol impairs female offspring glucose homeostasis and endocrine pancreatic development in the rat

Recent reports indicate that 7% of pregnant mothers in North America use cannabis. This is concerning given that in utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, causes fetal growth restriction and may alter replication and survival of pancreatic β-cells in the offspring. Accordingly, we hypothesized that maternal exposure to Δ9-THC during pregnancy would impair postnatal glucometabolic health of offspring. To test this hypothesis, pregnant Wistar rats were treated with daily intraperitoneal injections of either 3 mg/kg Δ9-THC or vehicle from gestational day 6 to birth. Offspring were subsequently challenged with glucose and insulin at 5 months of age to assess glucose tolerance and peripheral muscle insulin sensitivity. Female offspring exposed to Δ9-THC in utero were glucose intolerant, associated with blunted insulin response in muscle and increased serum insulin concentration 15 min after glucose challenge. Additionally, pancreata from male and female offspring were harvested at postnatal day 21 and 5 months of age for assessment of endocrine pancreas morphometry by immunostaining. This analysis revealed that gestational exposure to Δ9-THC reduced the density of islets in female, but not male, offspring at postnatal day 21 and 5 months, culminating in reduced β-cell mass at 5 months. These results demonstrate that fetal exposure to Δ9-THC causes female-specific impairments in glucose homeostasis, raising concern regarding the metabolic health of offspring, particularly females, exposed to cannabis in utero.     

Developmental alterations in maturing rats caused by chronic prenatal and postnatal diazepam treatments

The post treatment effects of early prenatal, late prenatal, early postnatal or combined prenatal and neonatal treatment with diazepam on the development of pain sensitivity, acoustic startle responsiveness, and benzodiazepine receptors in the cerebral cortex were investigated in rats between 14 and 90 days of age. Tail-flick latency was significantly decreased by combined prenatal and neonatal and by early prenatal diazepam treatment, but not by diazepam during the last half of gestation or during the neonatal period alone. Acoustic startle response was decreased by either late prenatal or neonatal diazepam treatment, but not by early prenatal treatment alone. Density of benzodiazepine receptors in the cortex was increased from postnatal day 1 to 21 by either early or late prenatal diazepam treatment. Neonatal diazepam treatment suppressed cortical benzodiazepine receptor or development until postnatal day 21; thereafter, receptor density increased to significantly higher values than in controls at 90 days of age. The results demonstrate that diazepam can alter development of pain sensitivity by actions during early gestation, startle responsiveness by actions late in pregnancy, and cortical benzodiazepine receptors by actions throughout gestation and the early postnatal period.     

Impact of Epigenetic Dietary Compounds on Transgenerational Prevention of Human Diseases

The etiology of most human diseases involves complicated interactions of multiple environmental factors with individual genetic background which is initially generated early in human life, for example, during the processes of embryogenesis and fetal development in utero. Early embryogenesis includes a series of programming processes involving extremely accurate time-controlled gene activation/silencing expressions, and epigenetic control is believed to play a key role in regulating early embryonic development. Certain dietary components with properties in influencing epigenetic processes are believed to have preventive effects on many human diseases such as cancer. Evidence shows that in utero exposure to certain epigenetic diets may lead to reprogramming of primary epigenetic profiles such as DNA methylation and histone modifications on the key coding genes of the fetal genome, leading to different susceptibility to diseases later in life. In this review, we assess the current advances in dietary epigenetic intervention on transgenerational human disease control. Enhanced understanding of the important role of early life epigenetics control may lead to cost-effective translational chemopreventive potential by appropriate administration of prenatal and/or postnatal dietary supplements leading to early disease prevention.     

Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring.     

Effects of maternal exposure to aflatoxin B1 during pregnancy on fertility output of dams and developmental,behavioral and reproductive consequences in female offspring using a rat model

A suboptimal in utero environment can have detrimental effects on the pregnancy and long-term adverse “programing” effects on the offspring. Aflatoxin B1 is one of the potent reproductive toxicants and currently detected in both milk and tissues. This article focuses on the effects of prenatal exposure to graded doses of aflatoxin B1 on the pregnancy outcomes of dams and postnatal developments of the female offspring, since these issues have ethological relevance in both animals and humans. Pregnant Wistar rats were injected intramuscularly with vehicle or aflatoxin B1 (10, 20, 50 or 100?μg/kg body weight/day) on days 12–19 of gestation. At parturition, newborns were observed for clinical signs of toxicity and survival. The female offspring were examined through a battery of tests in order to evaluate their developmental, behavioral and reproductive end points. All animals were born alive. The litter size of the aflatoxin B1 treated rats was comparable to the controls. However, the birth weight of the pups in the experimental group was significantly lower when compared to controls. Significant and persistent lags in cliff avoidance, negative geotaxis, surface rightening activity and ascending wire mesh, with a delay in elapsed time for vaginal opening were detected in the female progeny exposed to aflatoxin B1 during embryonic development. The locomotor activity and exploratory behavior in experimental females were significantly decreased than that of controls. Embryonic exposure to aflatoxin B1 also resulted in prolonged stress response, irregular estrus and suppressed fertility output in the progeny at their adulthood. These results indicate that in utero exposure to aflatoxin B1 severely compromised postnatal development of neonatal rats and caused irregular estrus that was accompanied by suppressed fertility output.     

Adverse reproductive effects of maternal low‐dose melamine exposure during pregnancy in rats

Melamine is a heterocyclic, aromatic amine and nitrogen‐enriched environmental toxicant, found in not only adulterated foodstuffs but also industrial household tableware and paints. Previous studies demonstrated adverse effects of high‐dose melamine on human infants and pregnant animals, but effects of low‐dose melamine on pregnancy have not been reported. In this study, reproductive effects of low‐dose melamine were investigated in pregnant rats. Melamine in the range of 12.5–50 mg/kg was administered to pregnant rats at different gestational stages. Maternal weight gain was not significantly affected, and other maternal morbidity was not observed. Low‐dose melamine exposure during pregnancy increased fetal size but reduced somite number in gastrulation (GD8.5–GD10.5) and organogenesis (GD10.5–GD16.5) periods, and increased incidence of stillbirth in whole gestational period (GD0.5 to delivery). Embryotoxicity of melamine was further confirmed by whole embryo culture in vitro that melamine retarded embryonic growth, impaired development of brain and heart, and induced open neural tube and atrioventricular defects with increased apoptosis. In conclusion, adverse reproductive effects of low‐dose melamine during pregnancy were identified in the developing rat embryos and the perinatal effects of melamine were gestational and developmental stage dependent. Detailed hazard and risk assessment of melamine in reproduction system are warrant. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 131–138, 2017.     

Fetal and offspring arrhythmia following exposure to nicotine during pregnancy

Although recent studies have demonstrated prenatal nicotine can increase cardiovascular risk in the offspring, it is unknown whether exposure to nicotine during pregnancy also may be a risk for development of arrhythmia in the offspring. In addition, in previous studies of fetal arrhythmia affected by smoking, only two patterns, bradycardia and tachycardia, were observed. The present study examined acute effects of maternal nicotine on the fetal arrhythmia in utero, and chronic influence on offspring arrhythmia at adult stage following prenatal exposure to nicotine. Nicotine was administered to pregnant ewes and rats. In the fetal sheep, intravenous nicotine not only induced changes of fetal heart rate, but also caused cardiac cycle irregularity, single and multiple dropped cardiac cycles. Although maternal nicotine had no influence on fetal blood pH, lactic acid, hemocrit, Na⁺, K⁺ levels and plasma osmolality, fetal blood PO₂ levels were significantly decreased following maternal nicotine in ewes. In offspring rats at 4–5 months after birth, prenatal exposure to nicotine significantly increased heart rate and premature ventricular contraction in restraint stress. In addition, arrhythmias induced by injection of nicotine were higher in the offspring prenatal exposure to nicotine in utero. The results provide new evidence that exposure to nicotine in pregnancy can cause fetal arrhythmia in various patterns besides tachycardia and bradycardia, the possible mechanisms for nicotine‐induced fetal arrhythmia included in utero hypoxia. Importantly, following exposure to nicotine significantly increased risk of arrhythmia in the adult offspring. The finding offers new insight for development of cardiac rhythm problems in fetal origins. Copyright © 2009 John Wiley & Sons, Ltd.     

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.     

Tissue levels of saccharin in the rat during two-generation feeding studies

A single oral dose of [³H]saccharin was given to female rats in late pregnancy. The concentrations of ³H in the tissues of fetal rats 6 to 12 hr after the dose were lower than those in the mother. However, the concentrations in fetal tissues, including bladder wall, decreased more slowly, so that by 48 hr they exceeded the corresponding values obtained for maternal tissues, suggesting the possibility of accumulation during chronic intake. Despite this, the steady-state concentrations of saccharin in the liver and kidneys of fetuses from mothers fed a 5% saccharin diet ad libitum were lower than the corresponding materal values, while the concentrations in the fetal bladder were similar or slightly higher. The concentrations of saccharin in the tissues of rats in utero were not markedly higher than those found in adult F₁ animals. The turnover of saccharin in the fetuses of animals maintained on 5% saccharin diet was similar to that seen after a single dose. The results showed no evidence of excessive accumulation in the bladder wall or other tissues of male rats during in utero exposure or during lactation, which could explain the reported sex and generation specificity of the tumorigenic response.     

d-Amphetamine unmasks postnatal consequences of exposure to methylmercury in utero: methods for studying behavioral teratogenesis

Pregnant rats were given various doses of methylmercury (MM) at three different stages of gestation (Days 0, 7 or 14). Administration of 56% or 27% of the dose given on the first day (Day 0) of pregnancy to 7 or 14 day pregnant rats, respectively, resulted in equivalent concentrations of MM ni 19 day old feti and 1 day and 1 week old neonates. A single, 5 mg MM/kg, oral dose on Day 0, or its equivalent on Days 7 or 14 of gestation did not produce any signs of toxicity in pregnant dams or their offspring. Weight gain of pregnant dams, litter size, litter weights at birth or at weaning and gross physical appearance were not different amongst the various treated groups and their respective controls. Operant level of bar pressing and acquisition of a discrete trial autoshape task indicated no differences with respect to operant levels, rate of acquisition or asymptotic performance resulting from exposure to MM in utero. The operant (autoshaped) behavior showed sex related differences to the disrupting influence of d-amphetamine (d-A); females were significantly more sensitive than males. Moreover, both males and females whose dams were treated with MM on Day 0 or 7 of pregnancy were significantly less affected by the d-A when compared with controls. Offspring born to dams given MM on Day 14 of pregnancy did not show a differential effect of d-A. It is concluded that early prenatal exposure to low doses of MM can result in behavioral consequences subtle enough to require unmasking of the effects with psychotropic drugs. Additionally, periods may exist during development when the embryo or fetus is most susceptible to behavioral or functional teratogenic effects of exposure to chemical insult. The testing procedures used in these experiments were objective, automatic and amenable for use with relatively large sample sizes compared with other operant behavior analytical methods. They also lend themselves to appropriate parametric statistical analyses, a staunch requirement for behavioral toxicological and teratological studies.     

Chronic in utero buprenorphine exposure causes prolonged respiratory effects in the guinea pig neonate

Our laboratory studies the effects of in utero opioid exposure on the neonate. In this work we test the effects of chronic in utero exposure to buprenorphine on the neonate. Buprenorphine is a promising candidate for treatment of opioid addiction during pregnancy and it has been suggested to decrease the neonatal abstinence syndrome in human infants. In our guinea pig model, we focused not only on the respiratory effects of in utero exposure on the neonate, but also studied withdrawal signs in the neonate, a major concern of all opioid treatment during pregnancy. Pregnant guinea pigs were treated with daily subcutaneous injections of 0.1 mg/kg buprenorphine during the second half of gestation. We measured weight, locomotor activity and respiratory function in pups of ages 3 to 14 days. Respiratory response was recorded using a two-chamber plethysmograph, while pups were breathing either room air or 5% CO₂. Our results show that chronic in utero exposure to buprenorphine induces respiratory effects up to day 14 after birth, while earlier studies have shown that effects of either in utero methadone or morphine only persist in the first week after birth in the guinea pig model. These data provide important information for clinical trials of buprenorphine treatment suggesting that duration and severity of respiratory effects of in utero buprenorphine exposure should be monitored.     

In utero exposure to arsenite contributes to metabolic and reproductive dysfunction in male offspring of CD-1 mice

In utero exposure to arsenite (iAs) is known to increase disease risks later in life. We investigated the effect of in utero exposure to iAs in the drinking water on metabolic and reproductive parameters in male mouse offspring at postnatal and adult stages. Pregnant CD-1 mice were exposed to iAs (as sodium arsenite) in the drinking water at 0 (control), 10 ppb (EPA standard for drinking water), and 42.5 ppm (tumor-inducing dose in mice) from embryonic day (E) 10–18. At birth, pups were fostered to unexposed females. Male offspring exposed to 10 ppb in utero exhibited increase in body weight at birth when compared to controls. Male offspring exposed to 42.5 ppm in utero showed a tendency for increased body weight and a smaller anogenital distance. The body weight in iAs-exposed pups continued to increase significantly compared to control at 3 weeks and 11 weeks of age. At 5 months of age, iAs-exposed males exhibited greater body fat content and glucose intolerance. Male offspring exposed to 10 ppb in utero had higher circulating levels of leptin compared to control. In addition, males exposed to 42.5 ppm in utero exhibited decreased total number of pups born compared to controls and lower average number of litters sired over a six-month period. These results indicate that in utero exposure to iAs at either human relevant concentration or tumor-inducing concentration is a potential cause of developmental origin of metabolic and reproductive dysfunction in adult male mice.     

Safety of infliximab use during pregnancy

Infliximab is a chimeric IgG1 monoclonal antibody to tumor necrosis factor alpha (TNF)-α used in the treatment of inflammatory bowel disease and rheumatoid arthritis. Infliximab does not actively cross the placenta during the first trimester, but undergoes efficient placental transfer during the late second and third trimesters and is detectable in the infant's serum for several months after birth. This raises concerns about immunological risks of infection and response to vaccines. Available evidence from registry studies and case reports involving more than 300 pregnancy outcomes suggest that infliximab carries low fetal risk and is compatible with use during conception and the first two trimesters of pregnancy. The long-term effects of infliximab exposure on the developing immune system are yet unknown. Based on limited data from several case reports, infants born with detectable levels of infliximab do not seem to have an increased risk of infections in their first year of life and have normal responses to nonlive vaccines. However, a fatal case of disseminated mycobacterial infection has been reported in an infant who received BCG vaccine at 3 months of age, to a mother who had been treated with infliximab throughout her pregnancy. Vaccination with live viruses should be postponed in infants exposed to infliximab in utero, until serum levels are undetectable which may require more than 6 months. Discontinuing infliximab early in the third trimester should be considered in order to minimize late fetal exposure.     

Intrauterine position and postnatal growth in Sprague-Dawley rats and ICR mice

In rodents, steroid hormones are thought to be transported between adjacent fetuses, and male or female fetuses that develop in utero between female fetuses may have higher serum levels of estradiol, and lower serum levels of testosterone, relative to siblings of the same sex that develop between two male fetuses. The consequence in the variation of postnatal growth, development, and function in the intrauterine position, using various parameters such as anogenital distance, preputial separation and vaginal opening, estrous cycle, locomotor activity, and growth of reproductive organs, were examined in Sprague-Dawley rats. ICR mice were treated with 17beta-estradiol before copulation and during pregnancy to address the interaction with endogenous estradiol during pregnancy. In rats, no evidence of effects of prior intrauterine position was observed for any of the parameters examined. Mouse fetal exposure via the mother to low-dose 17beta-estradiol revealed no changes in the rate of postnatal growth in males and females that developed in any intrauterine position in utero. The results of this study suggested that the intrauterine position of the embryos/fetuses did not affect the postnatal growth of the reproductive organs, sexual maturation, or behavior in rats and mice.     

Clara细胞分泌蛋白在新生儿外周血中的表达

目的探讨新生儿血CCSP与胎龄、呼吸道疾病的关系。方法 63例新生儿根据胎龄分为3组,23～29妊娠周、30～36妊娠周和足月儿。采用ELISA试剂盒测定血CCSP的水平,分析血CCSP的水平与新生儿呼吸道疾病的关系。结果 23～29妊娠周、30～36妊娠周早产儿血CCSP水平较低,足月儿血CCSP水平较高,出生后3～4d血CCSP水平升高,出生后7d血CCSP水平下降,呼吸道疾病患儿血CCSP水平下降。结论新生儿出生后血CCSP水平显著升高,CCSP可能对新生儿出生后早期肺损伤有保护作用。     

Sex differences in effects on sexual development in rat offspring after pre- and postnatal exposure to triphenyltin chloride

Consumers are exposed to organotin compounds (OTCs) via contaminated fish and seafood due to the accumulation of these compounds in marine organisms. Certain OTCs are immunotoxic and may also have endocrine disrupting properties resulting in adverse effects on the reproductive tract in mollusks and mammals. Since effects of in utero exposure to endocrine disrupting chemicals on the reproductive system are dependent on the critical window of exposure during its development, we conducted a comprehensive study with the aim to identify the most sensitive window of exposure to TPTCl and to investigate the effects of pre- and postnatal treatment on sexual development in rats. Male and female offspring rats were exposed to 2 or 6 mg TPTCl/kg b.w. and day either in utero and during lactation (gestation day 6 until weaning on PND 21) or from gestation day 6 until termination. As previously reported, offspring in the 6 mg TPTCl dose group exhibited high perinatal mortality and therefore no further evaluation was carried out at this dose level (Grote, K., Hobler, C, Andrade, A.J.M., Wichert Grande, S., Gericke, C., Talsness, C.E., Appel, K.E., Chahoud, I., 2007. Effects of in utero and lactational exposure to triphenyltin chloride on pregnancy outcome and postnatal development in rat offspring. Toxicology 238, 177–185). In the present paper, results on postnatal development obtained from surviving offspring of dams exposed to 2 mg TPTCl/kg b.w. are reported. Male offspring were sacrificed on PND 64 or 65 and female offspring at first estrus after PND 58. A clear sex difference in response to treatment was observed. Male postnatal development was severely affected with decreases in body weight gain, reproductive organ weights and testosterone concentration as well as a significant delay in the age at preputial separation. In contrast, females exhibited a precocious completion of vaginal opening while all other endpoints were unaffected. Most of these effects were already present in animals that were only exposed until weaning indicating that these effects may be irreversible and continued treatment until termination had contributed less than expected to the severity of the observed effects. The results of the present study suggest that the sensitive window for the evaluated endpoints seems to be the period of prenatal development and that male offspring rats were more susceptible to treatment.     

Low-level prenatal exposure to nicotine and infant neurobehavior

ObjectiveTo examine the association between prenatal exposure to nicotine from tobacco smoke and infant neurobehavior using tobacco biomarkers and a sensitive and comprehensive measure of infant neurobehavior.Study designParticipants were 318 infants (206 White, 95 Black, 17 Other) and their mothers. Prenatal tobacco smoke exposure was measured twice during pregnancy and once at delivery using maternal serum cotinine. Infant neurobehavior was assessed with the NICU Network Neurobehavioral Scale at approximately 5 weeks after birth.ResultsPrenatal tobacco smoke exposure was significantly associated with infant neurobehavior after controlling for important covariates, but the specific behaviors associated with exposure varied by race. In White infants, higher cotinine was associated with increased arousal (p = .030) and excitability (p = .034), and decreased self-regulation (p = .010). In contrast, among Black infants, higher cotinine was associated with decreased arousal (p = .001), excitability (p = .021), and special handling required to complete the assessment (p = .003), and increased self-regulation (p = .021) and hypotonicity (p = .016). In secondary analyses, we found racial differences in the effects of postnatal exposure to second hand smoke and low-level prenatal exposure.ConclusionsLow-level prenatal tobacco smoke exposure is associated with infant neurobehavior at 5 weeks of age, but the specific effects differ by race. These effects may reflect racial differences in nicotine metabolism that are similar to differences reported in adult and child studies of tobacco.     

Prenatal melamine exposure induces impairments of spatial cognition and hippocampal synaptic plasticity in male adolescent rats

Our previous studies showed that chronic melamine exposure could affect hippocampal synaptic plasticity and impair learning and memory on adult rats. In this study, we investigated whether prenatal melamine exposure (PME) induced cognitive deficits and impairment of synaptic plasticity in postnatal offspring. An animal model was produced by melamine exposure throughout gestational period with 400 mg/kg/day, while male offspring rats were employed. Rats’ performance in Morris water maze (MWM) was tested to evaluate learning and memory. To examine the variations of paired-pulse facilitation (PPF) and synaptic plasticity, field excitatory postsynaptic potentials (fEPSPs) were recorded in hippocampal CA1 by stimulating Schaffer collaterals path. The result showed that PME probably impaired spatial learning and memory. The fEPSPs amplitudes of LTP were much lower and the PPF ratio was significantly higher in PME group than controls. These data suggested that PME impaired hippocampal synaptic function, which was partly involved in spatial cognition impairments.