Effects of estrogenic compounds on neonatal oocyte development

In the mouse, oocytes develop in germline cysts that undergo breakdown resulting in primordial follicles, consisting of a single oocyte surrounded by granulosa cells. During this process, approximately two-thirds of the oocytes die. Exposure of female mice to environmental estrogens can alter oocyte development, limiting the number of primordial follicles that can be used for reproduction. Here we asked whether exposure to synthetic estrogens, diethylstilbestrol, ethinyl estradiol and bisphenol A affected perinatal oocyte development. Neonatal mice were injected with a low or high dose of each compound on postnatal days (PND) 1-4 and ovaries analyzed on PND5. Cyst breakdown, oocyte survival and follicle development were altered. The percentage of single oocyte was reduced from 84% in controls to 50-75%. The oocyte number per section was increased from 8 to 12-16. Follicle activation was reduced with 62% primordial follicles in controls to over 80% in most cases.     

Effects of fluoride on Xenopus embryo development.

Fluoride was first associated with fetal malformation shortly after water fluoridation was initiated in the 1940s. Since many chemicals can interact directly with the embryo to cause malformation, the effects of fluoride on embryonic and fetal development were investigated. The effects of sodium fluoride on the development of frog embryos were studied under conditions described by the Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a screening assay for teratogens. The most prominent malformations caused by sodium fluoride are reduction in the head-tail lengths and dysfunction of the neuromuscular system of the tadpoles. The values for LC50, EC50, and minimal concentration to inhibit growth (MCIG) of sodium fluoride met the limits established for a teratogen in frog embryos, showing that sodium fluoride is a direct acting teratogen on developing embryos. Since FETAX has a high degree of success in identifying mammalian teratogens, the observed teratogenic action of sodium fluoride on frog embryos would indicate a strong possibility that sodium fluoride may also act directly on developing mammalian fetuses to cause malformation.     

Effects of litter size on behavioral development in mice

The effect of litter size on behavioral development was investigated in 1384 offspring from 114 litters of CD-1 control mice. Litters were classified in four groups of size: 5 to 7 (I), 8 to 10 (II), 11 to 13 (III), and 14 to 17 (IV). Group III was regarded as the control group. The offspring were examined for behavioral development including surface righting at Postnatal Days (PND) 4 and 7, negative geotaxis at PNDs 4 and 7, cliff avoidance at PND 7, swimming behavior at PNDs 4 and 14, and olfactory orientation at PND 14. In behavioral development, surface righting at PND 7 was significantly affected in group I. Swimming direction at PND 4 was significantly affected in group IV, and those effects showed significant tendencies to be retarded as litter size increased. Other measured parameters showed no significant effect of litter size.     

免疫抑制剂对实验性矽肺的影响研究

目的：探讨免疫抑制剂对矽肺发病的影响。方法：动物采用随机法，分对照组，免疫抑制组。石英粉尘非暴露式吸人4周后，测定肺巨噬细胞功能，气管、支气管、肺显微镜观察。结果：免疫抑制组肺巨噬细胞吞噬功能受到明显抑制，肺内细胞结节增多，肺细支气管等管壁增厚并胶原纤维增生。结论：免疫抑制剂可加重矽肺的病程。     

Effects of methylmercury on postnatal neurobehavioral development in mice

Eighty ICR mice were randomly assigned to one of four groups given daily intraperitoneal injections of 0, 0.1, 1 or 3 mg/kg MeHg chloride respectively from postnatal days (PD) 15–17, and then tested with the Morris water maze on PD45. After that the mice were sacrificed by cervical dislocation, and the protein levels of NMDA receptor subtypes in the hippocampus were measured by Western blot analysis. A significant increase in the latency (F = 2.88, P < 0.05) before finding the platform was observed in the 1 and 3 mg/kg MeHg exposure groups. Further, the 3 mg/kg MeHg exposure group also had a longer swim distance (F = 2.97, P < 0.05) for finding the platform. In the probe test, the MeHg exposure groups displayed a smaller number of platform crossings when the hidden platform was moved, but this did not reach statistical significance. Western blot analysis results showed significant increases in the levels of NR1, NR2A and NR2B proteins of the hippocampus in the 1 and 3 mg/kg MeHg exposure groups. Overall, the current study found that MeHg exposure at 1 and 3 mg/kg doses during the postnatal brain growth spurt induces subtle and persistent learning deficits, and the neurobehavioral abnormalities of MeHg-exposed mice might be ascribed to alteration of the gene expression of specific NMDA receptor subunits in the hippocampus.     

胎儿铅暴露对婴儿情绪发育的影响

目的研究宫内铅暴露对日后婴幼儿情绪发育的影响,探讨导致婴儿情绪障碍的原因。方法选取足月新生儿脐带血测量血铅,并按照脐血铅含量分3组,A组为血铅0￣200μg/L,B组为血铅￣500μg/L,C组为血铅>500μg/L。追踪观察这3组新生儿9个月时的情绪发育情况,同时做关于情绪和社会适应能力(ASQ)的问卷调查,比较不同脐血铅对婴幼儿情绪发育的影响。结果3组间的ASQ分值差异有统计学意义(P<0.01),且随着血铅值的升高,ASQ分值也越高(分值和情绪发育呈负相关)。结论胎儿铅暴露在一定程度上可以造成日后婴幼儿情绪发育和社会适应能力的异常。     

Effects of prenatal carbon monoxide exposure on cardiac development

Biochemical assays and weight measurements were made to determine the basis for the cardiomegaly which has been reported following chronic carbon monoxide (CO) exposure. Long Evans rats bred in the laboratory were exposed throughout gestation either to room air or air containing 150 ppm CO. The exposure terminated within 12 hr after parturition. CO-exposed neonates showed persistent body weight depression throughout the preweaning period. Wet heart weight was elevated in the CO-exposed rats at birth, but no difference between groups remained at 4 days of age. Dry heart weight did not differ significantly between groups at birth. Biochemical analyses conducted at 1 day of age suggested a general reduction in concentration of protein as well as DNA, RNA, and free nucleotides although none of these differences was statistically significant. Total content of these cellular constitutents was not significantly affected by the prenatal CO exposure despite the increased wet weight of the heart. It is concluded that increased water content accounted for the increased heart weight seen at birth in CO-exposed rats.     

Effects of silver nanoparticles prenatal exposure on rat offspring development

Many types of nanocomposites employed in food packaging are based on silver nanoparticles (AgNP) because of their antibacterial properties, which can increase food shelf-life. As the commercialization of AgNP products has been expanding, the released of such nanoparticles in the environment has caused enormous concern, once they can pose potential risks to the environment and human beings. For instance, exposure of the maternal environment to nanomaterials during pregnancy may impact the health of the dam, fetus and offspring. In this context, here we investigated the effects of prenatal exposure of AgNP on the pregnancy outcomes of dams and postnatal development of their offspring. Pregnant Wistar rats were exposed to distinct AgNP concentrations (0, 1, 3 and 5 μg/kg/day) from beginning to the end of pregnancy. At parturition, newborns were observed regarding clinical signs of toxicity and survival rate. The offspring was examined by evaluating developmental endpoints. A delay in time for vaginal opening and testes descent were detected in the offspring exposed to AgNP during embryonic development. Our results indicate that prenatal exposure to AgNP can compromise neonatal rats’ postnatal development, especially the reproductive features.     

Effects of glycerol formal on embryonic development in the rat

The embryotoxic and teratogenic potential of glycerol formal, a solvent used in pharmacological and toxicological experimentation, was investigated in gravid Sprague-Dawley or Wistar rats on Days 6 through 15 of gestation. At dose levels of 0.25 – 0.50 and 1.00 ml/kg im, sc, and po, glycerol formal induced elevated postimplantation loss rates and a decrease of mean fetal weight in treated groups as compared to control groups. At 0.50 and 1.00 ml/kg im, sc, and po, glycerol formal induced elevated malformation rates. Malformations were mostly limited to cardiovascular defects, particularly ventricular septal defects, and wavy ribs. The embryotoxic and teratogenic effects appeared to be related more to dose and strain of rats used than to route of administration or to any particular day or days of treatment. Maternal toxicity was negligible.     

Effects of maternal chlorpromazine on offspring nervous system development.

Administration of chlorpromazine (7 mg/kg/day) to rat dams from day 8 of pregnancy until the pups were weaned produced small but statistically significant decreases in litter size and birth weight. The difference in pup weight was no longer present at the time of weaning. The offspring of chlorpromazine-treated dams were less able to maintain body temperature in response to restrained cold stress as determined when they were 60–65 days of age. They also incorporated significantly less¹⁴C from tyrosine into heart norepinephrine during acute cold exposure. No differences in incorporation of ¹⁴C into norepinephrine from tyrosine were evident when the animals were not subjected to cold stress. Similarly treated offspring did not have an increase in superior cervical ganglion tyrosine hydroxylase activity after 48 hr of cold exposure while the offspring of control dams did have a significant increase in the activity of this enzyme. These data suggest that maternal administration of chlorpromazine produces a permanent alteration in the ability of the offspring to respond to cold stress and that this deficit is related to an alteration in nervous system development.     

Effects of organolead compounds on rat embryonic and fetal development

Tetraethyl lead (TEL) and tetramethyl lead (TML) and trimethyl lead chloride (TriML), were found to be essentially nonteratogenic in Sprague-Dawley rats. Oral doses of TEL (7.5, 15, or 30 mg/kg), TML (40, 80, 112, or 160 mg/kg) and TriML (15, 30, or 38 mg/kg) were administered as 3 divided doses during early organogenesis (days 9, 10, and 11) or late organogenesis (days 12, 13, and 14), the day of positive sperm being day 1. In addition, TriML was administered iv at doses of 20, 28, 33, or 40 mg/kg on individual gestation days 8 through 15 inclusive. The highest dose of each compound in each experiment was lethal to the maternal animal. Lower dose levels produced typical slight to severe maternal organolead toxicity, dependent upon dose. Embryo or fetal toxicity was observed to accompany the administration of the organolead compounds and was characterized by growth retardation and delayed ossification of bone. Marked fetal effects were observed only in maternal animals that exhibited severe organolead toxicity and were, therefore, severely debilitated.     

视黄酸核受体在脑发育中的作用及机制

维生素A(vitamin A,VA)是人体必需的重要微量营养素,它在人体的视觉、免疫、生长发育及细胞分化等方面发挥广泛的生理学效应,一直都是营养学界研究的热点。VA的作用主要通过其体内活性代谢产物视黄酸(retinoic acid,RA)介导两大类视黄酸核受体：RARs(retinoic acid receptors)和RXRs (retinoid-X re-     

Effects of androstenedione on in utero development in rats.

This study was conducted to characterize the effect of androstenedione on estrous cyclicity, mating behavior and fetal development. Thirty-day old rats received corn oil alone or androstenedione (in corn oil) at one of four concentrations (0, 1.0, 5.0, 10.0 or 30.0 mg/kg body weight) by gavage for two weeks prior to mating, during the mating period and throughout gestation. Dose related increases in serum androstenedione, estradiol and estrone were observed in all androstenedione treated animals at gestation day 20. A statistically significant increase in serum testosterone concentration was observed in the 30 mg/kg dose group. Feed and fluid consumption were not affected by androstenedione treatment during the pre-mating or gestational periods, however a statistically significant decrease in the number of females with regular estrous cycles was observed in the 10.0 and 30.0 mg/kg dose groups. Exposure to androstenedione did not affect mean body weight gain during pre-mating or gestation. Slight not statistically significant reductions in the number of implants, number of viable fetuses and number of viable male fetuses were observed in the 30.0 mg/kg androstenedione group. Reductions were not observed in the number of corpora lutea. Fetal growth in terms of fetal weight, crown-rump length, anogenital distance and the number of external abnormalities was not affected by androstenedione exposure. At the doses given, androstenedione had no specific effect on the development of individual bones, including sternebrae. Dose related effects of androstenedione were not observed on the development of soft tissues. A statistically significant increase in moderately enlarged ureter at the kidney was observed in both the 1.0 and 5.0 mg/kg dose groups. Organ weights (expressed per gram of body weight or per gram of brain weight) were not affected by androstenedione treatment.     

Effects of orotic acid on the development of morphine tolerance

A marked tolerance to both analgesic and cataleptic effects of 20 mg/kg morphine hydrochloride was developed in rats during treatment with daily doses increasing from 20 to 120mg/kg s.c. within 11 days. Daily administration of 100 mg/kg sodium orotate i. p. 14 days before and during treatment with morphine significantly accelerated the development of tolerance for cataleptic as well as analgesic effects of morphine. The disappearance of the tolerance phenomena was delayed in the orotate-treated animals. No influence of orotate, however, could be observed on the formation of stereotyped behaviour and disappearance of stereotype.The results support the assumption, that morphine tolerance may be an adaptive process in the CNS realized by RNA and protein syntheses in different neuronal cell populations. Treatment with the RNA precursor may improve this process, perhaps by enhancing RNA synthesis.This research was supported by the Ministerium für Wissenschaft und Technik der DDR.     

Effects of zearalenone on in utero development in rats.

Zearalenone (ZE), an estrogenic mycotoxin produced by Fusarium graminearum or F. roseum, is one of the most common contaminants of cereal grains world-wide. The objective of this study was to determine the effects of ZE on in utero development of rats. Pregnant female Charles River Sprague-Dawley rats were gavaged once daily with ZE (in corn oil) at doses of 0, 1, 2, 4, or 8 mg/kg body weight on gestation days (GD) 6-19. All females survived to cesarean section on GD 20. At cesarean section, reproductive and developmental parameters were measured and blood was taken for hormone analysis. Dose-related decreases were seen in maternal feed consumption and body weight gain in all treated groups. Delayed fetal development was linked to maternal toxicity. Fetal body weight was significantly decreased in both sexes in all treated groups. ZE retarded skeletal ossification at 4 and 8 mg/kg. Fetal anogenital index (anogenital distance normalized for body weight) was increased in all treated groups, indicating an androgenic effect of ZE during fetal development. Fetal viability was significantly decreased at 8 mg/kg; significant decreases were observed in number of viable fetuses, and number of litters totally resorbed. At 4 and 8 mg/kg, maternal liver-body weight ratios were significantly increased and organ-brain weight ratios for weights of liver, heart, spleen, kidneys, and ovaries were significantly decreased. Gonadotropins (LH, FSH, and prolactin) and sex steroids (progesterone and estradiol) were analyzed from the blood serum obtained at cesarean section. LH in the 0, 1, 2, and 4 mg/kg groups showed minimal variation, and slightly increased at 8 mg/kg. FSH was decreased in the 1, 2, and 4 mg/kg groups, but the level at 8 mg/kg was slightly higher than the control level. Prolactin level was not affected at 1 mg/kg, slightly increased at 2 and 4 mg/kg, and significantly increased at 8 mg/kg. Progesterone was decreased at 2, 4, and 8 mg/kg and the decreases were significant at 2 and 4 mg/kg. Estradiol level was not affected at 1mg/kg, but dose-related decreases were observed at 2, 4, and 8 mg/kg. Only the 8 mg/kg level of estradiol was significantly decreased. In summary, ZE was maternally toxic and fetotoxic but not teratogenic. The increased anogenital distance observed in male and female fetuses was considered a hormonal change rather than a teratologic response. The increased anogenital distance indicated an androgenic effect. Based on the dose-related maternal and fetal toxicity in all treated groups, the NOEL for reproductive and teratogenic effects was less than 1 mg/kg.     

妊娠中晚期接触可卡因对小鼠胎儿神经系统发育的影响

目的　观察妊娠母体接触可卡因引起的胎儿神经系统发育异常 ,研究宫内暴露可卡因引起的胎儿发育迟缓是否与母体孕期营养不良有关以及胎儿神经系统发育异常与神经递质的变化之间的关系。方法　小鼠妊娠d 8(E8)到d 17(E17) ,每日 2次颈背部皮下注射盐酸可卡因 2 0mg·kg-1·d-1,同时建立饮食对照组和盐水对照组 ,每日 2次注射生理盐水 2 0ml·kg-1·d-1,在此期间记录各组母鼠、胎鼠生理指标。E17取材 ,用HPLC法检测给药组血中可卡因浓度及各组母鼠、胎鼠纹状体多巴胺 (dopamine ,DA)、5 羟色胺 (sero tonin ,5 HT)的浓度。结果　可卡因给药组 (COC)与盐水对照组 (SAL)相比 ,母体体重增长量及总摄食量均减少 ,纹状体多巴胺和 5 羟色胺含量增高 (COCn =16 ,SALn =11,P<0 0 1) ;胎鼠体重、脑重、纹状体重也存在明显差异 (SALn=76 ,COCn =92 ,P <0 0 1)。而可卡因给药组与饮食对照组 (SPF)相比 ,在母鼠摄食量相等、体重增长量无明显差异 (COCn =16 ,SPFn =12 ,P >0 0 1)的情况下 ,胎鼠的各项生理指标均下降 (COCn =92 ,SPFn =6 5 ,P <0 0 1) ,且脑纹状体多巴胺、5 羟色胺水平明显升高 ,分别为 (88± 12 )ng·g-1,(2 4 2± 18)ng·g-1。结论　宫内暴露可卡因可引起子代神经系统发育异常 ,这种发育异常?     

Effects of sevin on development of experimental estuarine communities.

The composition of animal communities developing from planktonic larvae in aquariums. A marked increase in the abundance of the annelid Polydora ligni in aquariums containing sand and flowing estuarine water was altered in the presence of the carbamate insecticide Sevin (carbaryl). Treatments were control and concentrations of Sevin that averaged 1.1, 11.1, and 103 micrograms/l; each treatment was replicated 8 times. Animals that colonized aquarium sand were collected in a 1-mm mesh sieve after 10 wk of exposure. Mollusks' arthropods, annelids, and nemerteans were the numerically dominant phyla. The average number of species per aquarium was significantly less (alpha = 0.05) in aquariums containing 11.1 or 103 micrograms/l than in those containing 1.1 micrograms/l or in control aquariums. The abundant clam Ensis minor grew significantly less in length at the higher concentrations of Sevin. The amphipod Corophium acherusicum was particularly affected; significantly fewer were found at all concentrations than in the control aquariums containing 103 micrograms/l corresponded to a marked decrease in the number of other annelids and to a significant absence of nemerteans.     

Effects of intrauterine infection or inflammation on fetal lung development

Intrauterine infection or inflammation is common in cases of preterm birth. Preterm infants are at risk of acute respiratory distress as a result of lung immaturity; evidence of exposure to infection and/or inflammation before birth is associated with a reduced risk of neonatal respiratory distress syndrome (RDS). Experimentally induced intrauterine inflammation or infection in sheep causes a precocious increase in pulmonary surfactant in the preterm lungs that improves preterm lung function, consistent with the reduced risk of RDS in human infants exposed to infection and/or inflammation before birth. The effects of intrauterine inflammation on fetal lung development appear to result from direct action of proinflammatory stimuli within the lungs rather than by systemic signals, such as the classical glucocorticoid-mediated lung maturation pathway. However, paracrine and/or autocrine production and/or metabolism of glucocorticoids in fetal lung tissue may occur as a result of inflammation-induced changes in the expression of 11β-hydroxysteroid dehydrogenase (types 1 and 2). Likely candidates that mediate inflammation-induced surfactant production by the preterm lung include prostaglandin E(2) and/or other arachidonic acid metabolites. Intrauterine inflammation induces the expression of enzymes responsible for prostaglandin production in fetal lung tissue. Inhibition of prostaglandin production prevents, at least in part, the effects of inflammation on fetal lungs. Our experiments are identifying mechanisms of surfactant production by the preterm lungs that may be exploited as novel therapies for preventing respiratory distress in preterm infants. Elucidation of the effects of inflammation on the fetal lungs and other organs will allow more refined approaches to the care of preterm infants exposed to inflammation in utero.