Long-lasting Effect of Maternal Hyperphenylalaninemia during Pregnancy on Postnatal Brain Development of Mice: Biochemical and Morphological Studies

Abstract The effect of maternal hyperphenylalaninemia on postnatal brain development was examined. Maternal hyperphenylalaninemia was induced by giving chow supplemented with 6% phenylalanine (Phe.) and 0.12% p-chlorophenylalanine (PCPA) for at least one month before coupling and then throughout pregnancy. Offspring from hyperphenylalaninemic mothers were given a normal diet from the first day after birth.
Infant mice were killed on the 21st, 28th and 56th day after birth. The protein, RNA and DNA in the brain were measured to determine the biochemical changes. Maturation of the dendrite of pyramidal cells was also examined by the Golgi method. The body weight of the offspring born to mothers, which had been treated with Phe. and PCPA during pregnancy, was significantly less than that of the control. The gain of cerebral weight showed a similar pattern with that to the body weight.
The total protein, RNA and DNA contents in the cerebrum of the treated group were also reduced significantly on 21st, 28th and 56th days after birth. The dendritic arborization of the cortical pyramidal neurons in the layer V showed significant reductions in the offspring born to hyperphenylalaninemic mothers compared with the age-matched control at 21, 28 and 56 days after birth.
These findings suggest that maternal hyperphenylalaninemia during pregnancy causes an irreversible retardation of the neuronal maturation both biochemically and morphologically, and subsequently gives rise to disorders of the higher cortical functions.     

Fetal growth retardation due to maternal tobacco smoke exposure in the rat

Smoking during pregnancy results in offspring with an average birth weight 200 g less than those of non-smoking mothers. The pathogenesis of this effect is still unknown and there is no general agreement about the causal relationship between maternal smoking and subsequent fetal growth retardation. In the present study, a model of maternal smoking during pregnancy in the rat was established using the P & I Walton Exposure Machine. The study consisted of three groups: control, pair-fed, and smoke-exposed. Smoke-exposed animals were exposed continuously to tobacco smoke for cycles of 7 min, 16 times a day from d 5 to d 20 of gestation. On d 21 of gestation, fetuses from all groups were removed by cesarean section, weighed, and dissected. The fetal brain, liver, and lungs as well as the placentas were weighed and analyzed for nucleic acid content. Fetal weight was found to be significantly reduced in both pair-fed and smoke-exposed groups compared with the control group. There was also a significant reduction in fetal body weight of the animals in the smoke-exposed group in comparison to those in the pair-fed group. Exposing the mother to smoke affected neither fetal brain weight nor nucleic acid content whereas fetal liver and lungs showed a significant decrease in both weight and nucleic acid content. These results indicate that the fetal growth retardation associated with maternal exposure to tobacco smoke in the rat corresponds to a disproportionate type.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidermal growth factor administered in pregnancy has little effect on placental, fetal and postnatal growth and development in rats

Biosynthetic human epidermal growth factor (EGF) was injected daily into female rats (40 micrograms/rat/day) on days 14-20 of pregnancy in two experiments. Number in litter was significantly greater in EGF- than in vehicle-treated mothers in experiment 1 but not experiment 2. Number in litter affected fetal weight. When this factor was taken into account statistically, there was no significant effect of EGF treatment on fetal weight or placental weight, DNA and protein concentrations at 21 days of gestation; nor was birth weight affected by treatment. However, growth in body weight postnatally from 4 to 115 days was slightly but significantly depressed in the offspring of the EGF-treated mothers. A negative effect of additional EGF in pregnancy on subsequent milk production is postulated. The timing of attainment of developmental milestones in the offspring was not affected.     

Pregnancy outcome in the Psammomys obesus gerbil on low- and high-energy diets

INTRODUCTION: Diabetes mellitus (DM) during pregnancy is associated with an increased risk for poor reproduction and a high rate of congenital malformations. The gerbil Psammomys obesus is a unique model for nutritionally induced Type 2 DM (T2DM) that enabled us to study the outcome of uncontrolled T2DM during pregnancy. METHODS: Female Psammomys on low-energy (LE) or high energy (HE) diet were studied. The blood glucose levels and weights of pregnant animals were determined. The offspring from the different groups were followed-up to weaning. RESULTS: Most of the HE-diet animals were diabetic (77%). There were no differences in the pregnancy rates in animals on both diets (32.7% in HE vs. 38.3% in LE). Pregnancy of the HE-diet group was longer than the LE-diet group (26.7 vs. 26.1 days), and litter average was reduced (2.7 vs. 3.0). At birth, the offspring of the HE-diet dams weighed less (5.2 vs. 7.2 g) and had smaller crown rump length (4.0 vs. 4.6 cm) These offspring also presented a 1-3 days delay in neuro-developmental parameters (first turn over, hair appearance, eye-opening and response to noise). However, from the fourth week of life they became diabetic, and from the third week they weighed more than the LE offspring. CONCLUSION: HE-diet caused diabetes, maternal complications and altered reproduction in Psammomys animals. The offspring of diabetic Psammomys presented birth weight and length changes as well as developmental delay.     

Effects of maternal smoking during pregnancy on body composition in offspring

Background: The aim of the present cross‐sectional study was to use objective methods to assess the association between maternal smoking and body composition in offspring. Methods: A total of 2508 grade 4 school children were enrolled; all underwent lifestyle disease and passive smoking screening. Children were classified into four groups according to their urinary cotinine level and maternal smoking status during or before pregnancy. Items measured on lifestyle disease screening were compared among the four groups. Results: Only degree of obesity (DO) and body mass index (BMI) were significantly associated with maternal smoking during pregnancy. The prevalence of both DO >20% and DO >30%, and BMI >22% and BMI >25% was highest in children of mothers who smoked during pregnancy. These children had a tendency toward shorter height and increased weight although it was not statistically significant. There were no significant differences between maternal smoking status and lipid profile among groups. Confounders such as food, exercise and sleep were able to be eliminated Conclusion: Maternal smoking during pregnancy may be an independent risk factor of changing body composition in offspring, that is, shorter height and increased weight.     

The effects of prenatal exposure to structurally diverse chemicals on the ontogeny of rat dehydrogenases

Activity levels of sorbitol dehydrogenase (SDH), lactate dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G6PDH) were measured in the livers and brains of rats treated prenatally with 3,4,3',4'-tetrachlorobiphenyl (4CB, 3 mg/kg/day), diethylstilbestrol (DES, 10 micrograms/kg/day), zeranol (ZN, 4mg/kg/day), and cadmium (Cd, 25 mg/kg/day) and compared with enzyme levels for control groups. Enzyme activities were measured at days 15, 17, 19, and 21 prenatally, and days 1, 5, 10, 21, 35, and 56 postnatally. SDH activity was not altered by treatment with 4CB, DES, or ZN, but Cd produced reduced levels in both liver and brain of sexually mature offspring. The patterns of LDH and G6PDH, including sexual differentiation of the latter in adult liver, were not affected by any of the treatments in either tissue. The developmental profiles of each of these enzymes in untreated animals is unique, suggesting that a similar catalytic mechanism is not a factor in determining the patterns of their developmental accumulation.     

邻苯二甲酸二(2-乙己基)酯导致隐睾症发生跨代遗传的机制研究

目的 探讨增塑剂邻苯二甲酸二(2-乙己基)酯(DEHP)于性腺发育的关键时期作用于孕鼠(0),研究F1-F3代隐睾跨代遗传的演变情况及各代睾丸基因组DNA甲基化转移酶水平的改变情况.方法 妊娠SD大鼠随机分为两组:正常对照组和DEHP实验组,实验组自妊娠第七天(GD7)到第十九天(GD19)持续经口予以DEHP 750 mg·kg-1 ·d-1灌胃,观察子代隐睾发生情况,雌鼠受孕率;记录大鼠体重和睾丸、附睾重量以及AGD值,观察精子数量和质量;观察连续三代大鼠睾丸组织形态的演变情况,检测DNA甲基化转移酶变化情况.结果 孕鼠在孕期(GD7-GD19)暴露于DEHP,第一代(F1)隐睾发生率为30％,第二代(F2)隐睾发生率为12.5％,第三代(F3)未见隐睾发生;交配实验F1代受孕率50％,F2代75％,F3代100％;HE染色发现F1代睾丸生精上皮明显萎缩,生精细胞少,F2代有所改善,F3代形态趋于正常.Real Time-PCR、免疫组化和Western Blot表明DNA甲基化转移酶的表达随着遗传代数的增加而上调,差异有统计学意义.结论 DEHP损伤大鼠雄性生殖功能,通过改变DNA甲基化转移酶的表达,继而导致基因组印记甲基化修饰模式改变并遗传给下一代,从而使子代雄性生殖系统发育的关键性印记基因作用失衡,并最终导致子代产生隐睾,可能是导致生殖系统损害的重要毒理机制之一.     

New Approach in Behavioral Teratology—Experimental Study on FAS *

ABSTRACT Fetal alcohol syndrome is known as an effect given by mothers. In connection with this, we so far observed rats from physical, biochemical, histological, and functional standpoints. Recently we observed synaptogenesis in brain together with behavior and learning ability of rats. Ethanol was given to mother rats during pregnancy and nursing periods, and learning ability of their offspring at 12 weeks of age was studied by the radial arm maze method. Also synaptogenesis in the hippocampus CA1 was observed at 2, 7, 14, 21, and 70 days of age by quantitative electron microscopy. The offspring were significantly deficient in learning ability tested with the maze compared with offspring of mother rats not exposed to ethanol. Densities of all synapses in the strata radiatum and lacunosum-moleculare of CA1 in the hippocampus became significantly lower at every time of the observation. Both axo-spinous and axo-shaftic synapses significantly decreased. Thus we found that observations of learning ability agreed with observations of synaptogenesis in the hippocampus CA1 which has important association with memory. This fact suggests that both observations will be of great value in the research in behavioral teratology.     

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目的探讨孕妇肥胖对婴儿体格发育和瘦素质量浓度的影响。方法武汉大学人民医院儿科于2002年1月至2003年6月选择肥胖孕妇和正常体重孕妇各80例,比较她们的子代在出生后及满1岁时的体重、身高和血清瘦素质量浓度;瘦素检测使用双抗体夹心ELISA法。结果符合检测数据统计条件的肥胖组为53例,正常组49例。(1)肥胖孕妇的瘦素质量浓度明显高于正常体重孕妇(P<0·01);(2)肥胖孕妇组子代出生体重和脐血瘦素质量浓度明显高于正常组(P<0·01);(3)肥胖孕妇组子代1岁时体重和血清瘦素质量浓度明显高于正常组子代(P<0·05)。结论孕妇肥胖对婴儿的体重和瘦素质量浓度有明显的影响,此影响对子代以后的生长发育和瘦素质量浓度是否继续存在还需要进一步的研究。     

大鼠不同时期高脂饮食对子代糖脂代谢的影响及机制研究

目的 探讨Sprague-Dawley母鼠不同时期高脂饮食对子代糖脂代谢的影响及相关机制。 方法 根据孕前及孕期哺乳期饮食的不同,将母鼠随机分为4组（n=9）：CC组（孕前、孕期哺乳期均正常饮食）、HC组（孕前高脂饮食、孕期哺乳期正常饮食）、CH组（孕前正常饮食、孕期哺乳期高脂饮食）、HH组（孕前、孕期哺乳期均高脂饮食）;子代生后3周断奶后,全部给予正常饮食。记录母鼠孕前、孕期体重及仔鼠体重。取各组幼年期（3周）、成年期（12周）雄性仔鼠,检测空腹血糖（glucose,GLU）、胰岛素（insulin,INS）及肝脏三酰甘油（triglyceride,TG）、总胆固醇（total cholesterol,TC）水平,计算胰岛素抵抗指数（homeostasis model assessment of insulin resistance,HOMA-IR）、糖耐量试验（glucose tolerance test,GTT）及胰岛素耐量试验（insulin tolerance test,ITT）的曲线下面积（area under the curve,AUC）;取肝脏组织行苏木精-伊红染色和油红O染色,观察肝脏脂质沉积;检测肝脏糖脂代谢关键基因IR、IRS、AKT和FASN、SREBP1c、PPARα的mRNA及其蛋白表达水平。 结果 孕前高脂饮食组（HC组、HH组）母鼠体重较正常饮食组（CC组、CH组）显著增加（P<0.001）;HC组、CH组、HH组母鼠孕期增重较CC组显著增加（P<0.001）。生后3周时,HC组、CH组、HH组的仔鼠体重、肝脏TG及TC含量,以及FASN、SREBP1c、PPARα的mRNA及其蛋白表达水平均较CC组显著增加（P<0.05）,肝脏脂质沉积增加,其中HH组增加最显著;HH组的空腹GLU及INS水平、HOMA-IR、GTT-AUC、ITT-AUC及肝脏p-IRS蛋白表达水平均较CC组显著增加,肝脏IR、IRS的mRNA及其蛋白表达水平均较CC组显著降低（P<0.05）。生后12周时,HC组、CH组、HH组的仔鼠体重、空腹GLU及INS水平、HOMA-IR、GTT-AUC、ITT-AUC、肝脏TG及TC含量、p-IRS蛋白表达水平,以及FASN、SREBP1c、PPARα的mRNA及其蛋白表达水平均较CC组显著增加（P<0.05）,肝脏脂质沉积增加,其中HH组增加最显著;HC组、CH组、HH组IR、IRS、AKT的mRNA水平均较CC组显著降低,IR、IRS、p-AKT蛋白表达水平均较CC组显著降低（P<0.05）。HC组与CH组在不同时期的糖脂代谢水平未见显著性差异（P>0.05）。 结论 大鼠怀孕前后不同时期的高脂饮食对子代的糖脂代谢具有不同的影响,孕前、孕期、哺乳期全程高脂饮食对子代糖脂代谢影响最大;大鼠高脂饮食对其子代糖脂代谢的影响考虑与糖脂代谢基因的表达改变有关。 引用格式:     

Development of Na+-K+-ATPase in neonatal rat brain synaptosomes after perinatal protein malnutrition.

Four protein dietary groups of rats were used in this study, namely: 27% casein diet fed throughout gestation and lactation (group C-C); 27% gestation, 10% lactation (group C-D); 10% gestation, 27% lactation (group D-C); 10% throughout gestation and lactation (group D-D). Mean body weight of group D-D at warning was 19 g compared with 59 g for group C-C. The specific activity of Na+-K+-ATPase in isolated synaptosomes from cerebral and cerebellar tissues increases throughout the lactation period. At 1 and 7 days of age no differences in Na+-K+-ATPase activity are noted in the brain regions of Groups C-C and D-D. At 14 and 21 days, however, the specific Na+-K+-ATPase activity was significantly reduced in isolated synaptosomes from both brain regions of the protein-deprived group. ATPase activity in cerebellar synaptosomes from dietary exchange groups (C-D and D-C) developed to the same extent as that of the control group (C-C) after 21 days of lactation. ATPase activity in the cerebral synaptosomes of the dietary exchange group (C-D) did not develop to the same extent as that in the control group (C-C) and the other dietary exchange group (D-C).     

Fetal rat adrenal growth and steroidogenesis in vitro after maternal dexamethasone treatment.

Two groups of female rats were treated with dexamethasone phosphate (DEX) for 24 h. One group received DEX in drinking water (10 micrograms/ml) on the 15th day of pregnancy (DEX15--16), and the second group on the 17th day of pregnancy (DEX 17--18). The mothers and fetuses were sacrificed on the 20th and 22nd days of pregnancy. DEX reduced adrenal weights and concentration of corticosterone in plasma of the treated females and their fetuses. Fetal body weight was also reduced. However, the lightest adrenal glands were found in fetuses of the DEX17--18 mothers. Furthermore, the 19-day-old fetuses belonging to the DEX17--18 mothers had smallest amounts of corticosterone in plasma, and in plasma, and their adrenal glands produced the lowest amounts of radioactive corticosterone, 11-doxycorticosterone and 18-hydroxy-11-deoxycorticosterone from 4-14C progesterone after 1 h or incubation in vitro. In the 21-day-old fetuses belonging to both the groups of treated mothers, the production of steroids by the adrenal glands was similar and to the same extent reduced in comparison to the control fetuses.     

Alteration in anxiety‐related behaviors and reduction of serotonergic neurons in raphe nuclei in adult rats prenatally exposed to ethanol

It is known that the developing serotonergic system is one of the targets of ethanol teratogenicity. Because serotonin has multiple functions in both mature and immature brains, disturbance of the serotonergic system by ethanol exposure in utero can be cause of a wide range of psychiatric problems in adulthood. In the present study, we observed serotonergic neurons in the midbrain raphe nuclei and anxiety‐like behaviors which would be affected by an altered serotonergic system in adult rats prenatally exposed to ethanol. Pregnant rats were fed a liquid diet containing 2.5–5.0% (w/v) ethanol on gestational days 10–21. Their offspring were examined at 60–70 days of age. A significant decrease in the number of serotonergic cells in the midbrain raphe nuclei was shown in prenatally ethanol‐exposed offspring. In an open field test, they spent more time in a central area compared to controls. Also in an elevated plus maze test, prenatally ethanol‐exposed offspring spent more time on the open arms than controls. These behavioral results suggested that prenatally ethanol‐exposed rats were less sensitive to anxiety. However, 44% of prenatally ethanol‐exposed offspring exhibited freezing behavior on the open arms of the elevated plus maze, causing strong anxiety, compared with 0% in intact control and 12.5% in isocaloric sucrose‐fed control groups. These findings suggest that prenatal ethanol exposure decreases both susceptibility and resistance of anxiety. Insufficient serotonergic actions caused by reduced serotonergic neurons in the raphe nuclei might contribute to the alterations in anxiety‐related behaviors observed in our prenatally ethanol‐exposed rats.     

The effect of experimental maternal hypoxia on fetal lung growth

Timed-pregnant rats at a gestational age of 14 days were exposed to 10% ambient oxygen (normobaric hypoxia) and compared to pair-fed animals of the same gestation and controls fed ad libitum. The lungs of the offspring were analyzed morphometrically and biochemically at day 21 of gestation after cesarean section. The hypoxic mothers and the pair-fed mothers showed similar diminution of weight gain and their fetuses showed growth retardation, more so in those of the hypoxic mothers. The lung volumes and weights were significantly different in the offspring of hypoxic and pair-fed mothers compared to those of mothers fed ad libitum. However, the lung volume and lung weight to body weight ratios were not different between groups, including pair-fed and hypoxic, and lung size was proportional to the amount of general growth segment in all. Morphometric analysis showed the volume proportion of saccular air, saccular wall, conducting airways, and nonparenchyma to be the same in each group. The gas exchanging surface areas were also the same. Dry lung weight, DNA, and protein per lung were decreased in the offspring of hypoxic mothers compared to the two other groups. The issue of whether the offspring of the hypoxic mothers should be regarded as having specific hypoplasia because of diminished cell number is discussed.     

Lower maternal folate status in early pregnancy is associated with childhood hyperactivity and peer problems in offspring

Background: Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring. Methods: In a prospective cohort study, maternal red blood cell folate (RCF) was measured at 14 weeks of pregnancy and total folate intake (TFI) from food and supplements was assessed in early and late pregnancy. The offspring’s head circumference and body weight were measured at birth and in infancy, and 100 mothers reported on children’s behavioural difficulties at a mean age of 8.75 years using the Strengths and Difficulties Questionnaire. Results: Lower maternal RCF and TFI in early pregnancy were associated with higher childhood hyperactivity (RCF: beta = ?.24; p = .013; TFI: beta = ?.24; p = .022) and peer problems scores (RCF: beta = ?.28; p = .004; TFI: beta = ?.28; p = .009) in the offspring. Maternal gestational RCF was positively associated with head circumference at birth (adjusted for gestational age), and mediation analyses showed significant inverse indirect associations of RCF with hyperactivity/inattention and peer problems via fetal brain growth. Adjustment for mother’s smoking and drinking alcohol during pregnancy did not change the results. Conclusions: Although the associations are small and residual confounding is possible, our data provide preliminary support for the hypothesis that lower folate status in early pregnancy might impair fetal brain development and affect hyperactivity/inattention and peer problems in childhood.     

Maternal type 1 and gestational diabetes: postnatal differences in insulin secretion in offspring at preschool age

Background: It is well known that children born to mothers with diabetes in pregnancy are more likely to develop metabolic abnormalities in later life. Most prior studies have not differentiated between offspring of mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) or lack a control group of non‐exposed offspring. Subjects: Offspring of T1DM (n = 16), GDM (n = 22) and mothers without diabetes (n = 25) born at Oulu University Hospital. Aim: To assess insulin secretion and insulin resistance in the offspring of T1DM and GDM at preschool age in comparison with offspring of non‐diabetic mothers. Methods: Anthropometric measurements and intravenous glucose tolerance testing were performed. First‐phase insulin response (FPIR) and homoeostasis model assessment (HOMA) values were calculated. Pregnancy and birth data were analysed in relation to later metabolic parameters in all three groups using one‐way analysis of variance (anova ) and analysis of covariance (ancova ). Results: At a mean age of 4.9 yr, offspring of T1DM had increased fasting serum insulin concentrations (p = 0.044), FPIR (p = 0.034) and HOMA‐B values (p = 0.008) compared with offspring of GDM or with offspring of healthy controls (statistically non‐significant). The GDM gained least weight during pregnancy, and when adjusted for maternal weight gain during pregnancy, there were no statistically significant differences between study groups. Conclusions: Prenatal exposures to maternal type 1 and gestational diabetes may have different effects on postnatal glucose metabolism in the offspring assessed at a mean age close to 5 yr. Maternal weight gain in pregnancy may affect the postnatal glucose metabolism in the offspring.     

Effects of oxytocin treatment in early life on body weight and corticosterone in adult offspring from ad libitum-fed and food-restricted rats

The aims of this study were: (1) to assess the effects of maternal undernutrition during pregnancy on adult offspring with regard to growth, body composition and plasma levels of glucose, insulin and corticosterone, and (2) to investigate whether oxytocin treatment early in life could ameliorate the adverse effects of food restriction in utero. Pups from ad libitum-fed and food-restricted (60% of ad libitum intake during pregnancy) rats were injected subcutaneously once a day with oxytocin or saline on days 1-14 after birth. At adult age (62 days), male offspring from food-restricted dams had lower body weight, less adipose tissue, lower plasma glucose but higher corticosterone levels, compared to offspring from ad libitum-fed dams. However, oxytocin-treated food-restricted males had higher body weight, higher glucose and lower corticosterone levels compared to their saline-treated counterparts. In conclusion, oxytocin treatment early in life seems to ameliorate some of the adverse effects of food restriction in utero.     

Effects of maternal caffeine ingestion on the perinatal cerebrum

The cerebra of fetal rats from dams given 0.04 or 0.02% caffeine in drinking water ad libitum before and/or during pregnancy were examined on gestational day 21. A low placental weight was induced by caffeine ingestion for a long time throughout premating and pregnancy. A greater reduction in the fetal weight of the cerebrum than that of the body was observed with caffeine ingestion during pregnancy of levels of 1.5-3.0 micrograms caffeine/ml or g wet weight in dams and fetuses. In the cerebra of offspring, the levels of caffeine and theophylline did not change for 4 h after birth, and theophylline was not detected at all after intraperitoneal injection of caffeine. Thus, maternal caffeine should be warned against the fetal cerebral function.     

Prenatal Tobacco and Maldevelopment of the Brain*

ABSTRACT Maldevelopment of the brain in offspring whose mothers smoked during pregnancy is being evaluated and reviewed using our Japanese data. In addition to the criteria for the fetal tobacco syndrome (FTS), I proposed the term, “fetal tobacco effects (FTE)”, when the gestational age is <37 weeks. Maternal factors during pregnancy including coffee drinking or polydrug use, and malconditions, such as premature rupturing of the membranes or placental abnormalities, were present at higher frequencies in FTE than FTS, although the factors of smoking and light drinking during pregnancy did not differ between them. As an indicator of maldevelopment of the brain, CNS involvement was more frequent and severer in FTE than in FTS. These findings suggest that factors in addition to smoking causing reduction in the gestation period may contribute to CNS involvement. As to the concomitant effects of ethanol and tobacco on maldevelopment of the brain, CNS involvement was highest in the offspring of women who both smoked and drank heavily. In conclusion, based on the concept of FTE in addition to FTS, a causal relationship between prenatal smoking and maldevelopment of the brains of offspring has to be investigated, especially as to factors modifying the effects of tobacco during pregnancy.     

Effects of prenatal heat stress on postnatal growth, behavior and learning capacity in mice

Pregnant ICR mice were immersed in water at 42 or 43 degrees C for 10 min once or twice daily on days 12 through 15 of gestation and the postnatal development of their offspring was observed. Postnatal weight gain of the offspring and their brain weight at 11 weeks of age were smaller than the values for control animals. As compared with controls, prenatally heated mice were less active in an open field and learned slower in a water-filled multiple T-maze and in a shuttle box. Thus, prenatal brief hyperthermia in mice was shown to suppress the body and brain growth during the postnatal period and adversely affect their emotionality and learning capacity.