外源性核苷酸改善孕期饮酒小鼠雄性后代学习记忆能力的研究

目的探讨外源性核苷酸对孕期饮酒C57BL/6J小鼠雄性后代学习记忆能力的影响。方法 C57BL/6J孕鼠随机分为空白对照组、酒精对照组和低(0.01%)、中(0.04%)、高(0.16%)3个核苷酸干预组,酒精对照组和3个核苷酸干预组孕鼠于孕6～15d给予5g/kg体重酒精灌胃,3个核苷酸干预组另外给予相应剂量核苷酸强化饲料进行喂养,待仔鼠断乳后,每窝随机抽取2只雄性仔鼠,依次进行旷场、水迷宫、跳台和穿梭箱4个行为学实验,分别观察动物的空间认知能力、空间记忆能力、被动回避能力和主动回避能力。结果旷场实验结果显示,酒精对照组的中央格停留时间和穿格数明显少于中、高剂量组(P﹤0.05);Morris水迷宫实验结果显示,酒精组定位航行潜伏期普遍长于其他各组,实验d6与空白对照组和中、高剂量组差异有统计学意义(P﹤0.05和P﹤0.01),实验d7各组穿台次数差异无统计学意义(P﹥0.05);跳台实验结果显示,各组电击次数差异无统计学意义(P﹥0.05),酒精对照组训练时的潜伏期明显短于其他各组(P﹤0.05);穿梭箱实验结果显示,酒精对照组的主动回避时间显著短于空白对照组(P﹤0.01)、电击次数也明显比后者多(P﹤0.01),而中、高剂量组的主动回避时间也明显比酒精对照组长(P﹤0.05和P﹤0.01);低、中剂量组的电击次数多于空白对照组(P﹤0.05);各组电击时间的差异无统计学意义(P﹥0.05)。结论外源性核苷酸可能具有改善宫内酒精暴露C57BL/6J小鼠学习记忆能力的作用。     

甲基汞对子代小鼠生长发育的影响

甲基汞影响染毒雄鼠与正常雌鼠所产子代小鼠的生长发育。其影响程度与甲基汞染毒剂量有关。高剂量染毒组子代小鼠窝平均活胎数及子鼠出生时体重、身长和尾长明显低于阴性对照组（Ｐ＜０．０１）。子代小鼠生长发育缓慢，到性成熟后甲基汞对其生长发育影响更为明显，染毒各组子鼠体重均明显低于阴性对照组（Ｐ＜０．０２）。子代小鼠初级精母细胞染色体分析未见明显改变。     

不同剂量碘对小鼠子代生长发育影响的实验观察

[目的]观察不同剂量的碘化钾对小鼠子代生长发育的影响.[方法]将断乳后1个月的BALB/c小鼠随机分为5组(U、NI、5 HI、10 HI、50 HI),饮用不同浓度的含碘化钾水,饲养3个月后雌雄合笼,取子一代20、40日龄小鼠,观察不同日龄子鼠的体重、身长、尾长、后肢长及脑和各主要脏器的重量变化.[结果]与NI组比较.各日龄LI组仔鼠体重、身长、尾长、后肢长及脑的绝对重量明显降低(P＜0.05),而脑的相对重量增高(P＜0.01).各碘过量组与NI组比较无统计学差异(P＞0.05).[结论]碘缺乏会影响小鼠子代的生长发育,但是小鼠对高碘有极强的酎受力,当碘摄入量为正常的50倍以内时,不会影响小鼠子代的生长发育.     

不同剂量碘对小鼠子代生长发育影响的实验观察

[目的]观察不同剂量的碘化钾对小鼠子代生长发育的影响.[方法]将断乳后1个月的BALB/c小鼠随机分为5组(LI、NI、5HI、10HI、50HI),饮用不同浓度的含碘化钾水,饲养3个月后雌雄合笼,取子一代20、40日龄小鼠.观察不同日龄子鼠的体重、身长、尾长、后肢长及脑和各主要脏器的重量变化.[结果]与NI组比较,各日龄LI组仔鼠体重、身长、尾长、后肢长及脑的绝对重量明显降低(P<0.05),而脑的相对重量增高(P<0.01).各碘过置组与NI组比较无明显差异(P>0.05).[结论]碘缺乏会影响小鼠子代的生长发育,但是小鼠对高碘有极强的耐受力,当碘摄入量为正常的50倍以内时,不会影响小鼠子代的生长发育.     

高放射性矿泉水对小鼠生育力及子代生长发育的影响

为观察高放射性矿泉水对小鼠生育力及仔鼠生长发育的影响。按美国毒理研究机构提出的持续繁殖实验方法，观察受孕率、每窝生胎鼠数、生育平均间隔天数、性别比例、死胎与畸胎数及仔鼠生长发育等。结果显示：两种高放射性矿泉水均可导致胎鼠性别比例失调，出现雄鼠显著多于雌鼠的现象（Ｐ＜０．０１），其中一种矿泉水组还出现４只卷尾畸形胎鼠，提示高放射性矿泉水可能对实验动物的遗传物质具有一定的损伤作用，但对实验动物的一般健康状况及生长发育过程则未显示出不利的影响。     

高本底放射性饮水对小鼠生育力及子代生长发育的影响

根据美国毒理研究机构提出的持续繁殖实验的方法，观察高本底放射性饮水对小鼠生育力及仔鼠生长发育的影响。观察指标包括受孕率、每窝生胎鼠数、生育平均间隔天数、死胎畸胎数及仔鼠生长发育各种指标等。结果显示：高本底放射性饮水对实验动物生育力和胎鼠生长发育水平表现出一定的促进作用，其余检测指标均无统计学意义。     

外源核苷酸对小鼠免疫功能的影响

目的 :　本实验研究了日粮核苷酸促进免疫抑制小鼠的免疫功能恢复的作用。方法 :　选取 5～ 6 w龄 ,体重为 (2 0± 2 ) g的健康昆明种小鼠 6 0只 ,设 0、0 .0 5 %、0 .2 5 %三个核苷酸水平处理 ,每个处理中又分成正常和免疫抑制两个组 ,其中所有免疫抑制组在实验的第 2 d一次性大剂量腹腔注射环磷酰胺 (1 5 0 mg/kg bw) ,制备免疫抑制模型 ;正常组注射等同剂量的生理盐水。饲养 1 0 d后观察小鼠增重、脾脏和胸腺的脏器指数、脾淋巴细胞转化率、脾脏中抗 SRBC抗体形成细胞数量以及血清中抗 SRBC抗体水平。结果 :　日粮中添加核苷酸能够提高正常小鼠的增重 (P<0 .0 5 )、胸腺指数、淋巴细胞转化率 (P<0 .0 5 )及血清中抗体水平 ,极显著提高免疫抑制小鼠抗体水平 (P<0 .0 1 ) ,使抑制小鼠的各项指标接近正常。抗 SRBC抗体形成细胞数量没有显著变化。结论 :　在无核苷酸日粮中添加核苷酸能够促进正常小鼠免疫功能的提高 ,使免疫抑制小鼠免疫功能得到改善。     

砷氟对子代生长发育影响的研究

新疆奎屯地区由于地理地质的原因，造成该地区某些地下水中砷、氟蓄积，导致了饮用这些井水的居民出现地方性砷中毒和氟中毒[1，2]。已有研究结果[3－6]表明，砷、氟均可通过胎盘，影响胎儿及子代的生长发育，但仍然缺乏母体摄入高砷、高氟后对生后儿童青少年健康影响的流行病学调查研究的资料。我们于1995年7月对经1985年改水后出生在原砷、氟中毒病区的3～10岁儿童进行了生长发育情况的调查，以期了解母体摄入高砷、高氟水后对子代是否存有潜在危害。1对象与方法1．1对象：选择奎屯垦区123团房建连为A区（原为高砷、高氟区），原水砷含量…     

砷对小鼠子代生长发育的影响

我们研究了孕鼠接触砷对子代生长发育的影响，结果显示，染砷各组仔鼠机体砷和脑组织砷含量增高，大脑皮层神经细胞结构异常。０．７５ｍｇ／ｋｇ剂量组仔鼠表现为神经行为发育迟缓，外周血淋巴细胞α－醋酸萘酯酶（ＡＮＡＥ）阳性率降低．４．５０ｍｇ／ｋｇ剂量组仔鼠断乳后体重增长缓慢，血液胆碱酯酶活性降低，血清溶血素水平亦显著下降。表明砷可经母体影响胚胎和子代的生长发育。     

氟对小鼠子代生长发育的影响

观察结果显示，染氟各组仔鼠机体组织氟含量增高，大脑皮质神经细胞超微结构异常。０．４５ｍｇ／ｋｇ剂量组仔鼠已表现为体格和早期神经行为发育迟缓；而０．４５ｍｇ／ｋｇ剂量组３０日龄仔鼠血清溶血素水平显著增高。表明氟可经母体对仔鼠各系统的发育产生不同影响。     

出生前后铅暴露对婴幼儿生长发育的影响

对妊娠 3个月左右的孕妇开始进行追踪观察 ,并随访其子女至 2岁。在此期间分别采集孕妇和婴幼儿的血样做血铅分析。并对孕妇家庭的一般情况及分娩、婴幼儿喂养和发育情况进行调查。分析出生前后铅暴露水平对婴幼儿体格发育的影响。结果显示 :妊娠 9个月血铅和脐带血铅水平与出生后婴幼儿的身长、体重均呈负相关。多元回归分析显示幼儿于 1岁和 2岁时的身长和体重分别与同期血铅水平呈负相关 (P<0 .0 5 )     

Sexual orientation after prenatal exposure to exogenous estrogen

Thirty women aged 17 to 30 years with documented prenatal exposure to the nonsteroidal synthetic estrogen diethylstilbestrol (DES) were compared to thirty women of similar demographic characteristics from the same medical clinic who had a history of abnormal Pap smear findings. A subsample of the DES women were also compared to their DES-unexposed sisters. Sexual orientation in its multiple components was assessed by systematic semistructured interviews. In comparison to both control groups, the DES women showed increased bisexuality and homosexuality. However, about 75% of the DES women were exclusively or nearly exclusively heterosexual. Nonhormonal and hormonal interpretations of these findings are discussed.This research was supported in part by U.S.P.H.S. research grants MH-34635 (NIMH), Y01-CN-00711 (NCI), and MH-30906 (NIMH).     

Effect of prenatal exposure to ethanol on postnatal development of intestinal transport functions in rats

Summary.Background: Alcohol consumption by pregnant animals and humans leads to general growth impairment in their offspring, delayed growth and multiple birth defects collectively called Fetal Alcohol Syndrome. In utero exposure of ethanol to rat pups causes damage to their developing intestinal epithelium which leads to impairment of nutrient assimilation and growth retardation during postnatal development. Aim: To determine the effect of prenatal exposure of ethanol on the postnatal development of rat intestinal Na⁺-dependent and independent D-glucose transporter along with the amino acids (glycine and Lleucine) transporter activity at 4, 8, 14, 20 and 30 days of postnatal age. The changes in the expression levels of Na⁺-dependent glucose transporter (SGLT1) mRNA was assessed at different days of postnatal age in rat pups.Methods: Wistar strain albino female rats were fed ethanol at a dose of 2 g/kg body weight/day orally by Ryles tube for one month before mating and during the entire period of gestation while the control females received isocaloric glucose. Transport studies were performed using the everted intestine of 4, 8, 14, 20 and 30 day-old control and ethanol-exposed pups employing the tissue accumulation method. The expression of SGLT1 mRNA at different days of postnatal age in control and ethanol-exposed rat pups was determined using a Northern Blot analysis.Results: Prenatal exposure of ethanol to rat pups leads to a decrease in their body weight, intestinal length and weight and reduces the uptake capacities of SGLT1 as well as energy dependent glycine and L-leucine transporters with respect to their age-matched controls. However, the mRNA levels of SGLT1 remained unaltered in the ethanol-exposed pups at all ages of postnatal development compared to their controls.Conclusion: These findings suggest that in utero exposure to ethanol leads to a general delay in the postnatal development of the intestine of ethanol-exposed rat pups affecting mainly the development of intestinal energy dependent D-glucose and amino acid (glycine and L-leucine) transporters.     

Effects of prenatal ethanol exposure on iron utilization in the rat

The effects of prenatal ethanol exposure on iron metabolism in rat dams and pups were studied. Sperm-positive nulliparous dams were assigned to groups on the third day of gestation (G3): ET rats were fed a liquid diet containing 9% ethanol (v/v); PC rats were pair-fed a non-ethanol, isocaloric liquid diet; FC rats were fed the same nonethanol diet adlibitum. All animals were individually housed in stainless steel metabolic cages from G3 to G18 and transferred to polypropylene cages to await delivery. Food intake and dam body weight were significantly less in the ET and PC groups compared to the FC control group. Water intake was significantly greater in the ET dams than in controls. Gestation length was significantly increased in the ET rats only. Pup body weight was significantly decreased in the ET rats only compared to controls. Apparent absorption of iron in the ET dams was significantly greater than in the PC and FC dams. The inutero ethanol exposure resulted in a significant increase in liver and femur iron concentrations in the newborn pups when compared to the PC and FC control pups. The marked increase clue to understanding presence of liver pathology that has been reported to occur in children with fetal alcohol syndrome.     

Effects of prenatal ethanol exposure on ethanol-induced locomotor activity in rats

In adulthood, offspring with Fetal Alcohol Effects exhibit different responses to ethanol than nonexposed offspring; however, the majority of this research has utilized high levels of ethanol prenatally with resultant behavioural and/or physical anomalies. The present research focused on moderate prenatal ethanol exposure and subsequent challenge with low doses of ethanol. Following impregnation, female rats were exposed to between 3-4 g/kg of ethanol in a saccharin solution daily in a voluntary free-choice with water during one of each trimester or during all trimesters. There was a no-ethanol control group which received saccharin only as well as a group of foster dams who drank only water. At 30 days of age, male offspring were tested in an open-field after injection of either 1 g/kg ethanol or a comparable volume of saline. Rats exposed prenatally to ethanol in the second trimester showed enhanced locomotor activity. However, rats exposed prenatally to ethanol in either the first, third or during all trimesters showed no significant augmentation in activity. The results are discussed in terms of the adverse effects of moderate levels of prenatal ethanol exposure on fetal neurochemical development, specifically, the excitatory and inhibitory systems.     

Dose-dependent effects of prenatal ethanol exposure in the guinea pig

The guinea pig is an appropriate animal for studying ethanol central nervous system (CNS) teratogenesis due to its extensive prenatal CNS development. In order to establish an ethanol dosage regimen that produces CNS teratogenesis, the objective of this study was to characterize the dose-dependent effects of chronic ethanol administration on pregnancy outcome and locomotor activity of the offspring. Pregnant guinea pigs received one of the following oral treatments, via intubation into the oral cavity, throughout gestation: 3, 4, 5, or 6 g ethanol/kg maternal body weight/day; isocaloric sucrose and pair feeding; or water. The 5 and 6 g ethanol/kg/day regimens produced maternal death, spontaneous abortion, and perinatal death with at least 75% incidence; the 3 and 4 g ethanol/kg/day regimens produced little or no maternal, embryonic/fetal, or perinatal lethality. The 3 and 4 g ethanol/kg/day regimens did not affect other indices of pregnancy outcome compared with the respective isocaloric-sucrose pair-fed control animals and water-treated animals. The 3, 4, and 5 g ethanol/kg/day regimens increased spontaneous locomotor activity in the offspring, and there was a direct relationship between the magnitude of hyperactivity at days 10 and 60 of age and each of the ethanol dosage regimens and the maternal blood ethanol concentration on day 56 of gestation. The data demonstrate that, in the guinea pig, chronic oral administration of ethanol produces: (a) dose-dependent effects on pregnancy outcome, (b) hyperactivity in the offspring that is dose- (and maternal blood ethanol concentration-) and age-related, and (c) persistent hyperactivity into adulthood with minimal toxicity on pregnancy outcome for the 4 g ethanol/kg/day regimen.     

Effects of prenatal ethanol exposure on postnatal renal function and structure in the rat

Effects of prenatal ethanol exposure on postnatal renal function and structure in the rat. Renal function and morphology were studied in 90-day-old offspring of ethanol-fed (E) rats and were compared to pair-fed control (C) animals. Compared to C rats, E rats were smaller at birth, had higher fractional sodium excretion (p less than 0.01) and lower fractional potassium excretion (p less than 0.01). In E rats, sodium (Na) restriction resulted in a significant increase in urine flow and Na wastage, whereas C rats remained in Na balance. E rats developed hyperkalemia, when potassium (K) intake was increased from 2.8 to 14 mEq/day. Baseline creatinine clearance, urine and blood osmolalities and pH, plasma electrolytes and aldosterone concentrations were similar in both groups. There was no significant difference in wet or dry kidney weight, renal water content, or renal tissue concentrations of Na or K between the two groups. No difference was found in gross morphology or light microscopic appearances of the kidneys between E and C rats. Thus rats exposed to ethanol during fetal life have a defect in urine concentration and Na conservation when fed a low Na diet and a defect in K excretion when given a K load without evidence of any gross or light microscopic renal structural abnormalities at 90 days of age.     

Electrophysiology of hippocampal CA1 neurons after prenatal ethanol exposure.

In the present study, we examined the longitudinal effects of prenatal ethanol exposure on the electrophysiological characteristics of CA1 neurons in hippocampal slices. Hippocampal slices were obtained from young (25-32-day old) and adult (63-77-day old) male offspring of rats given one of four treatments during gestation. Three groups of pregnant rats were orally intubated with 0, 4, or 6 g/kg ethanol on gestational days 8-20. Caloric intake for the 0- (nutritional control) and 4-g/kg groups was yoked to that of the 6 g/kg group. A fourth group (untreated control) was not intubated, and was given ad lib access to food. Long-term potentiation and paired-pulse inhibition were unaffected by prenatal ethanol exposure in young and adult rats; however, slices taken from the young 6 g/kg ethanol group displayed a significantly lower maximal CA1 population spike amplitude evoked by Schaffer collateral stimulation as compared to young controls. This difference was not observed in adult animals. These data suggest that some aspects of hippocampal physiology are negatively affected in young rats as a result of prenatal ethanol exposure, but this effect reverses as the animal matures.     

Sex-dimorphic behavior in childhood subsequent to prenatal exposure to exogenous progestogens and estrogens

Thirteen boys and 15 girls with a history of prenatal exposure to medroxyprogesterone acetate only and 22 boys and 15 girls with exposure to a variety of progestogens and estrogens singly or in combination were studied at age 8–14 years in comparison to closely pair-matched, unexposed controls. This report concerns the findings on sex-dimorphic behavior as assessed by separate interviews with the child and his/her mother. Hormone-exposed boys and controls differed little, while in girls prenatal sex hormone treatment seemed to be associated with some degree of increased stereotypic femininity.This work was supported in part by grants from the Spencer Foundation, the William T. Grant Foundation, and the Ford Foundation, and by the following grants of the United States Public Health Service: NIMH Clinical Research Center Grant MH-30906, NIMH Research Grant MH-34635, and NCI Research Grant Y01-CN-00711.     

Influence of prenatal ethanol exposure on vascular contractile response in rat thoracic aorta.

Fetal alcohol syndrome is associated with cardiovascular malformation. However, the impact of prenatal ethanol exposure on vascular function is not clear. The purpose of this study was to examine the influence of prenatal ethanol exposure on vascular response in adulthood. Timed-pregnancy, female rats were fed an ethanol-containing liquid diet (36% calorically or 6.36% [vol./vol.]) or control diet from gestation day 2 until labor. The pups continued to receive a standard rat chow through adulthood, and the force-generating capacity of aortic ring segments was examined. Prenatal ethanol exposure did not significantly affect postnatal growth, but it did lead to elevated blood pressure in adulthood. The contractile response to potassium chloride was similar in vessels with intact endothelium, although the median effective concentration (EC(50)) was significantly reduced by prenatal ethanol exposure in rings with denuded endothelium. The response to norepinephrine was attenuated by prenatal ethanol exposure in rings with either intact or denuded endothelium. The endothelium-dependent relaxation to carbamylcholine chloride was significantly attenuated by prenatal ethanol exposure. Vasorelaxant response to the nitric oxide donor sodium nitroprusside or beta-adrenergic agonist isoproterenol was similar between control and prenatal-ethanol-exposed groups with either intact or denuded endothelium. Ethanol elicited a dose-dependent endothelium-dependent vasorelaxation, which was comparable between the two animal groups. The ethanol-induced endothelium-dependent vasorelaxation was attenuated by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester. These findings seem to indicate that prenatal ethanol exposure contributes to alterations of both endothelium-dependent and endothelium-independent vascular contractile responses.