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1.
Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.  相似文献   

2.
Pregnancy exposure to di(n-butyl) phthalate (DBP) in rats induces a testicular dysgenesislike syndrome (TDS) in male offspring. Earlier studies suggested altered Sertoli cell development/maturation may result, especially in testes that become cryptorchid. This study quantitatively assessed Sertoli cell numerical and functional development in DBP-exposed rats and compared (unilaterally) cryptorchid and scrotal testes. Pregnant rats were gavaged with 500 mg/kg/day DBP or corn oil from embryonic (E) Days 13.5 to 21.5. Male offspring were sampled on E21.5 or Postnatal Day 6, 10, 15, 25, or 90. Sertoli cell number in DBP-exposed males was reduced by approximately 50% at E21.5 but recovered to normal by Days 25-90, accompanied by significant changes in plasma inhibin B and testosterone levels. Sertoli cell maturational development in DBP-exposed males, assessed using five protein markers (anti-müllerian hormone, cytokeratin, androgen receptor, CDKN1B, and Nestin), was largely normal, with some evidence of delayed maturation. However, in adulthood, Sertoli cells (SC) in areas lacking germ cells (Sertoli cell-only [SCO] tubules) often exhibited immature features, especially in cryptorchid testes. Sertoli cells in DBP-exposed animals supported fewer germ cells during puberty, but this normalized in scrotal testes by adulthood. Scrotal and especially cryptorchid testes from DBP-exposed animals exhibited abnormalities (SCO tubules, focal dysgenetic areas) at all postnatal ages. Cryptorchid testes from DBP-exposed animals exhibited more Sertoli cell abnormalities at Day 25 compared with scrotal testes, perhaps indicating more severe underlying Sertoli cell malfunction in these testes. Our findings support the concept of altered Sertoli cell development in TDS, especially in cryptorchid testes, but show that maturational defects in Sertoli cells in adulthood most commonly reflect secondary dedifferentiation in absence of germ cells.  相似文献   

3.
On pregnancy day 12 101/H and CBA mice were injected intraperitoneally 2.5 mg/kg bw thiophosphamide. 3.5-month-old male offspring were sacrificed. The drug effect on the testes was evaluated by karyologic analysis of the germ cell generations on stage 7 of the seminiferous epithelium cycle. A reliable reduction in the number of spermatogonia A, preleptotene and pachytene spermatocytes and spermatids at development stage 7 was found in 101/H mice. There were interspecific differences in spermatogenesis intensity in intact animals and recovery of germ cell pool after thiophosphamide action inducing toxicity.  相似文献   

4.
邻苯二甲酸二(2-乙基己基)酯(di-2-ethylhexylphthalate,DEHP)及氯氰菊酯(cypermethrin,CYP)是我国广泛存在的两种环境内分泌干扰物(environmental endocrine disruptors,EEDs),具有显著的抗雄激素活性及生殖毒性,可致雄性性腺发育不良.祖国传统医学认为,性腺发育不良属肾精亏虚、肾气不足,临床采用益肾填精中药治疗取得显著疗效,但其具体机制尚不清楚.本实验主要研究益肾填精中药拮抗EEDs——DEHP及CYP引致青春前期大鼠性腺发育不良的作用机制.实验中染毒组分别饲喂500 mg/kg DEHP,80 mg/kg CYP及500 mg/kg DEHP+80 mg/kg CYP,治疗组采用40 mg/kg益肾填精中药与相应染毒物质同时饲喂.研究结果显示,DEHP、CYP单独及联合染毒组的青春前期大鼠睾丸重量、睾丸系数及血清睾酮水平均显著下调;睾丸氧化应激指标MDA含量、GSH-Px活性明显上升;病理组织及超微结构显示睾丸形态萎缩;睾丸支持细胞功能相关的基因与蛋白表达均出现不同程度的下调.益肾填精中药治疗干预后,睾丸重量、睾丸系数及血清睾酮水平均显著增加并接近对照组水平;睾丸形态明显改善,细胞数量增加;睾丸氧化应激水平下降;实时荧光定量PCR及Western印迹显示睾丸支持细胞功能相关的基因与蛋白的表达水平显著上调.本研究证实,益肾填精中药对DEHP及CYP的抗雄激素活性及生殖毒性有显著拮抗作用,可明显拮抗染毒物质诱导的氧化应激作用,促进睾酮分泌,并改善睾丸支持细胞功能,这可能是益肾填精中药有效拮抗EEDs抗雄激素活性及其生殖毒性的主要作用机制之一.  相似文献   

5.
Chen WJ  Kelly RB 《Life sciences》2005,76(11):1249-1258
Smoking during pregnancy causes intrauterine growth retardation and low birth weight of the offspring. However, it is unclear whether nicotine, rather than other compounds from a cigarette, would mediate long-term growth retardation. There is a body of evidence suggesting that optimal thyroid status is important for the normal development of the fetus. Therefore, these studies examined whether developmental nicotine exposure would interfere with the growth of the offspring and alter the thyroid status of neonates. Pregnant Sprague-Dawley rats were given 0, 15 or 25 mg nicotine pellets throughout pregnancy. Some offspring continued to receive 1 or 2 mg/kg/day nicotine during early postnatal period. The remaining offspring received no further treatment after birth. The body weight of all offspring was monitored until adulthood. Additionally, the neonatal thyroid status from all treatment groups was assessed from the serum of 10-day-old pups. Regardless of the timing of nicotine exposure, the nicotine treatment significantly increased the body weight in female offspring starting on postnatal day (PD) 35 and such an increase persisted into adulthood (PD 91). However, this nicotine exposure paradigm led to a transient increase in male offspring body weight on PD 35. Furthermore, current nicotine exposure regimens did not alter the total T4 level, T3 uptake and the calculated Free T4 index. The present findings are in agreement with some clinical studies reporting a higher body weight among children born to mothers who smoked during pregnancy. Furthermore, the data on thyroid status suggest that cigarette smoking-induced alterations in thyroid status might be mediated through compounds in cigarettes other than nicotine.  相似文献   

6.
OBJECTIVE: The purpose of this study was to examine whether gestational exposure to major environmental endocrine‐disrupting chemicals, nonylphenol (NP), would lead to nerve behavioral and learning and memory capacity alterations in the male offspring of rats, and reproductive development alterations in the male offspring of rats. METHODS: Dams were gavaged with NP at a dose level of 50 mg/kg/day, 100 mg/kg/day or 200 mg/kg/day daily from gestational day 9 to 15, and at a dose level of 40 mg/kg/day, 80 mg/kg/day or 200 mg/kg/day daily from gestational day 14 to 19 (transplacental exposures). RESULTS: Exposure to 200 mg/kg/day NP produced a significant decrease in learning and memory functions in offspring rats (P<0.05) in Morris water maze task, as demonstrated by the increased escape latency and number of error. In Step‐down Avoidance Test, offspring rats exposed to NP spent more reaction time (RT) and presented lower latency to first step‐down than the control offspring (P<0.01). In utero exposure to 80 and 200 mg/kg/day NP produced a significant decrease in the number of live pups per litter and ratio of anogenital distance to body length on PND 0 (P<0.05), and also testes and prostate weight, activities of ALP, plasma testosterone concentration, cauda epididymis sperm counts, daily sperm production et al. respectively on PND 90 (P<0.05). Histopathological examination of the brain biopsy illustrates that exposure to NP at high dose induces the presence of abnormal distribution of spermatozoa showed in lumina of the seminiferous tubules, and absence of spermatogenesis and spermiogenesis. CONCLUSION: Gestational exposure to nonylphenol might induce neurotoxic and reproductive toxic effects on F1 male rats. Birth Defects Res (Part B) 89:418–428, 2010. © 2010 Wiley‐Liss, Inc.  相似文献   

7.
The effects of the perinatal oral exposure to Gum Arabic (GA) on mice offspring was examined. GA was added to the drinking water of pregnant female Swiss–Webster strain mice at doses of 1 and 4 g/kg body weight, starting from the first day of pregnancy. The treatment continued until the fifteenth day after delivery, after which mothers were switched to plain tap water. A number of tests were carried out on offspring starting one day after birth and extending up to postnatal day 30 (PD30). Pups showed a reduced gain of body weight and delayed opening of the eyes in comparison to the control group and only pups exposed to 1 g/kg body weight GA had a faster appearance of hair. Sensory motor reflex tests carried out during the weaning period (from day of birth to PD21) showed enhanced motor reflexes in pups exposed to GA. During the adolescent period (from PD22 to PD30), offspring showed dose-dependent enhanced motor activity (on PD22), reduced anxiety and fear (on PD27) and slightly enhanced memory and learning abilities (on PD30). Biochemical tests of a number of blood parameters were conducted during and after the weaning period (on PD15 and PD30, respectively). Our results indicated that GA might have a hypoglycemic and a beneficial effect on red and white blood cell counts. This study gives a first insight on the effect of GA consumption on offspring, providing a starting point for further studies.  相似文献   

8.
Lipopolysaccharide (LPS) is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND) 26, anogenital distance (AGD), a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T) level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13–17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I–VI, increased the percent of seminiferous tubules in stages IX–XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.  相似文献   

9.
Although the adult mouse Leydig cell (LC) has been considered refractory to cytotoxic destruction by ethane dimethanesulfonate (EDS), the potential consequences of exposure during reproductive development in this species are unknown. Herein pregnant CD-1 mice were treated with 160 mg/kg on Gestation Days 11-17, and reproductive development in male offspring was evaluated. Prenatal administration of EDS compromised fetal testosterone (T) levels, compared with controls. EDS-exposed pups recovered their steroidogenic capacities after birth because T production by hCG-stimulated testis parenchyma from prepubertal male offspring was unchanged. However, prepubertal testes from prenatally exposed males contained seminiferous tubules (STs) devoid of germ cells, indicating a delay in spermatogenesis. In adults, some STs in exposed males still contained incomplete germ cell associations corroborating observed reductions in epididymal sperm reserves, fertility ratios, and litter size. Morphometry revealed an EDS-induced increase in interstitial area and a concomitant decrease in ST area, but stereology revealed an unexpected decrease in the number and size of the LCs per testis in exposed males. Paradoxically, there was an increase in both serum LH and T production by adult testis parenchyma, indicating that the LCs were hyperstimulated. These data demonstrate permanent lesions in LC development and spermatogenesis caused by prenatal exposure in mice. Thus, although adult mouse LCs are insensitive to EDS, EDS appears to have direct action on fetal LCs, resulting in abnormal testis development.  相似文献   

10.
If neurotransmitter balance is upset in the developing nervous system by exposure to antidepressant drugs, structural and functional hedonic phenotypes of offspring may be affected. In order to test this hypothesis, two groups of pregnant Wistar dams were exposed to vehicle or fluoxetine by implantation on gestational day 14 of osmotic minipumps delivering 0 or 10 mg/kg/day fluoxetine for 14 days. The consequences of perinatal fluoxetine exposure on offspring conflict-exploratory behavior were quantified using the elevated plus-maze on postnatal day (PND) 30. Beginning on PND 60, the reinforcing properties of acutely administered cocaine were examined using a place conditioning procedure. Beginning on PND 90, a subset of rats were implanted with jugular catheters and allowed to acquire self-administration of cocaine in an operant environment. In support of the hedonic modulation hypothesis, perinatal fluoxetine produced a significant decline in both nucleus accumbens cell count (-9%) and serotonin transporter-like immunoreactivity in the raphe nucleus (-35%) on PND 120. In the elevated plus-maze, perinatal fluoxetine exposure decreased (-21%) overall activity. In the place conditioning trial, only the fluoxetine-treated group exhibited a significant place preference for the compartment paired previously with cocaine. In a cocaine self-administration extinction trial, there was a statistically significant increase (350%) in extinction response rate among fluoxetine-exposed offspring. These findings suggest that perinatal exposure to fluoxetine perturbs adult serotonergic neurotransmission and produces a positive hedonic shift for conditioned reinforcing effects of cocaine.  相似文献   

11.
Bisphenol-A (BPA) has been shown to influence development of the brain and behaviors. The purpose of the present report was to investigate the effects of perinatal exposure to BPA on learning/memory and its mechanism of action, especially focusing on N-methyl-d-aspartate receptor (NMDAR). Perinatal maternal exposure to BPA at 0.5, 5, and 50 mg/kg/d significantly extended the escape length to find the hidden platform in Morris water maze, and BPA at 0.5 or 5 mg/kg/d markedly decreased the percentage of time spent in the quadrant where the platform had been during training both in postnatal day (PND) 21 and PND 56 mice. The results of passive avoidance test showed that the error frequency to step down from a platform after received footshock was significantly increased, and the latency of the step-down response onto the grid floor 24 h after received footshock was obviously reduced by exposure to BPA at 5 and 50 mg/kg/d (P < 0.01) in the PND 21 offspring or at 50 mg/kg/d in the PND 56 offspring (P < 0.01). Furthermore, perinatal exposure to BPA significantly inhibited the expressions of NMDAR subunits NR1, NR2A, and 2B in the hippocampus during the development stage, especially in PND 56 mice. The expressions of estrogen receptor beta (ERβ) in both PND 21 and PND 56 mice were markedly down-regulated by BPA at 0.5, 5, and 50 mg/kg/d. These results indicate that perinatal exposure to BPA affects normal behavioral development in both spatial memory and avoidance memory, and also permanently influences the behavior of offspring in adulthood. The inhibition of expressions of NMDAR subunits and ERβ in hippocampus during postnatal development stage may be involved.  相似文献   

12.
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disrupter. Currently, little is known about neurodevelopmental toxicity of DEHP in wildlife and humans. The present study investigated the effects of DEHP, focusing on the changes in the behavior of offspring mice at the ages of 6 and 12 w, respectively, following utero and lactational exposure to DEHP (10, 50, and 200 mg/kg/d) from gestation day 7 through postnatal day 21. The results of open field tasks showed that DEHP increased the grooming of males at age 6 w and females at age 12 w but decreased the frequency of rearing of 6-w-old females and the number of grid crossings of 12-w-old females. In the Morris water maze task, 50 and 200 mg/kg/d DEHP significantly prolonged the time of searching the hidden platform in water maze and reduced the time staying in the target quadrant during a probe trial of 6-w-old male mice, but not of 6-w-old females nor 12-w-old mice of both sexes, suggesting an impaired spatial learning and memory among younger males after perinatal exposure to DEHP. Western blot analyses further showed that DEHP at 50 and 200 mg/kg/d decreased the levels of the N-methyl-d-aspartic acid (NMDA) receptor subunits NR1 and NR2B in the hippocampus of 6-w-old males. These results suggest that uterine and lactational exposure to low doses of DEHP sex-specifically impacted behaviors, including locomotion activity and spatial memory, via the concomitant inhibition of the NMDA receptor of the hippocampus in offspring mice.  相似文献   

13.
On the 12th day of pregnancy CBA, 101/H and AKR mice were given thiophosphamide in a dose of 5 mg/kg bw, and were sacrificed on the 19th day of pregnancy. The action of thiophosphamide on embryonal ovaries and testes was studied by assaying for the population of oocytes and relative number of the different stages of meiotic prophase I; index of the degeneration germ cells; for the population of prospermatogonies and their degeneration; morphometric study of nucleus of nucleolus of prospermatogonies. A significant decrease of germ cells was found in male and female embryos on the 19th day of pregnancy after thiophosphamide injection. Interspecific differences were found as regards the number of germ cells and their proportion in health as well as in response to a single antenatal injection of thiophosphamide.  相似文献   

14.
15.
Monk BR  Leslie FM  Thomas JD 《Hippocampus》2012,22(8):1750-1757
Prenatal alcohol exposure leads to long-lasting cognitive and attention deficits, as well as hyperactivity. Using a rat model, we have previously shown that perinatal supplementation with the essential nutrient, choline, can reduce the severity of some fetal alcohol effects, including hyperactivity and deficits in learning and memory. In fact, choline can mitigate alcohol-related learning deficits even when administered after developmental alcohol exposure, during the postnatal period. However, it is not yet known how choline is able to mitigate alcohol-related behavioral alterations. Choline may act by altering cholinergic signaling in the hippocampus. This study examined the effects of developmental alcohol exposure and perinatal choline supplementation on hippocampal M(1) and M(2/4) muscarinic receptors. Sprague-Dawley rat pups were orally intubated with ethanol (5.25 mg/kg/day) from postnatal days (PD) 4-9, a period of brain development equivalent to the human third trimester; control subjects received sham intubations. From PD 4-30, subjects were injected s.c. with choline chloride (100 mg/kg/day) or saline vehicle. Open field activity was assessed from PD 30 through 33, and brain tissue was collected on PD 35 for autoradiographic analysis. Ethanol-exposed subjects were more active compared to controls during the first 2 days of testing, an effect attenuated with choline supplementation. Developmental alcohol exposure significantly decreased the density of muscarinic M(1) receptors in the dorsal hippocampus, an effect that was not altered by choline supplementation. In contrast, developmental alcohol exposure significantly increased M(2/4) receptor density, an effect mitigated by choline supplementation. In fact, M(2/4) receptor density of subjects exposed to alcohol and treated with choline did not differ significantly from that of controls. These data suggest that developmental alcohol exposure can cause long-lasting changes in the hippocampal cholinergic system and that perinatal choline supplementation may attenuate alcohol-related behavioral changes by influencing cholinergic systems.  相似文献   

16.
N, N1-bis (dichloroacetyl) diamine 1, 8-octomethylenediamine (WIN 18,446) is an experimental drug which was first investigated as a male contraceptive. It is soluble in lipid solvents but not in water. The administration of 1,200 to 1,600 mg/kg to pregnant rats on the tenth day of gestation produced multiorgan fetal malformations. Smaller doses, 400 to 800 mg/kg, especially if divided over 2 or 3 days, caused perinatal death. Thus, 60 to 100% of offspring of rats given WIN 18,446 on the tenth and 11th days of gestation died at birth or within 4 days (Taleporos et al., 78). The present study investigated such deaths. At doses of 200 mg/kg on day 10 or 50 mg/kg on days 10 and 11, 67% of offspring had defective or absent diaphragms, 48% had tracheobronchiomegaly with cystic lungs, and 67% had pleural hemorrhage. At doses of 100 mg/kg given on 1 day or 25 mg/kg each day for 2 days, 50% had tracheobronchiomegaly with cystic lungs and rudimentary acini. At lower doses (18.8 mg/kg X 2 or 12.4 mg/kg X 3), a majority of fetal lungs had rudimentary acini, thick septa, few capillaries, and wide cuffs of perivascular connective tissue. Thus, a chemical given during organogenesis produced dysgenesis of the respiratory apparatus. Varying the dose produced malformed lungs with persistently deficient acini which model such human lung faults as tracheobronchiomegaly (Mournier-Kuhn Syndrome; Mounier-Kuhn, '32), bronchiolar dysplasia (Wilson-Mikity Syndrome), and perinatal death with acinar failure resembling neonatal hyaline membrane disease.  相似文献   

17.
Effect of ethinyl estradiol on the differentiation of mouse fetal testis   总被引:5,自引:0,他引:5  
Y Yasuda  T Kihara  T Tanimura 《Teratology》1985,32(1):113-118
In an evaluation of the effect of ethinyl estradiol (EE) on the differentiation of fetal mouse testes, the ratio of the seminiferous tubular region to the testicular tissue region, the ratio of Sertoli cells to gonocytes in tubule cross sections, and the size of Leydig cells were determined by the Texture Analyse System (T.A.S., Leitz) in histological preparations of the testes. The testes were those of fetuses taken from dams given orally 0, 0.02, 0.2 or 2.0 mg/kg of body weight of EE in olive oil from day 11 through day 17 of gestation and killed at term. From experimental and the control testes, five sections were taken at 40-micron intervals. The areas of the seminiferous tubular region and the testicular region were determined and the Sertoli cells and gonocytes in tubule cross section were counted in each of the five sections. The diameters of 100 Leydig cells selected at random were averaged. These data were analyzed by Student's t test. The seminiferous tubular region was significantly increased in the testes treated with 0.02 mg/kg of EE and significantly decreased in those treated with 0.2 mg/kg of EE. The number of gonocytes per tubule cross section was significantly increased in the testes treated with 0.02 or 2.0 mg/kg of EE. The number of Sertoli cells per tubule cross section and the number of Sertoli cells per gonocyte were significantly decreased in the experimental testes. The size of the Leydig cells was significantly decreased in the testes treated with 0.2 mg/kg of EE. These findings suggest that prenatal exposure to EE before testicular differentiation affects tubular formation, the proliferation of fetal Sertoli cells, and Leydig cell differentiation, resulting in disturbances of spermatogenesis.  相似文献   

18.
12 1/2-15 1/2 day embryonic mouse testes of 129/terSv and CBA/T6T6 strains were transplanted under the kidney capsule of adult hosts. After 3-5 days in 41% of CBA/T6T6 transplants and in 82% of 129/terSv transplants a limit number of germ cells began meiosis. The percentage of meiotic germ cells was inversely related to the total number of gonocytes and the organization of seminiferous cords. The presented evidence indicates that the ability of the germ cells to begin meiosis precociously depends on: 1) genotype of donor embryos; 2) age of transplanted testis, and 3) using whole of half of gonad for transplantation. After 10-15 days in two out of 46 129/terSv testes (4%) growing oocytes were observed.  相似文献   

19.
Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.  相似文献   

20.
Phthalates are plasticizers finding wide spread use in industrial and household products, with measureable levels of phthalate-derived metabolites in the general US population. Phthalates have endocrine disruption potential and have been implicated as obesogens. Our exploratory investigation to reveal the impact of in utero exposure to a phthalate on the biochemical profiles of the brain, testes, and uterus of prepubertal offspring, and of tissues from dams administered butylbenzyl phthalate (BBP). Pregnant rats (three per group) were administered (on gestation day 14?C21) corn oil (control), or 25?mg/kg/day or 750?mg/kg/day BBP in corn oil. Tissues were collected from each of the dams on postnatal day (pnd) 21 (~3?weeks after the end of BBP administration), and from each of the pups on pnd 26 (~4 weeks after birth to dams administered vehicle or BBP during gestation) and processed for metabolomics analysis. Multivariate data analyses revealed metabolites that best distinguished the exposed and control groups. The metabolites most important to distinguishing the study groups were tested for significance using the exact Wilcoxon rank-sum test. Male pups had significant differences (control versus BBP dose groups) in levels of metabolites for both the brain and testes even at the P?<?0.01 level. However, female pups and dams had significant testing for the uterus only at the P?=?0.1 level tested. Female pups also had some significant differences for the brain with P values between 0.5 and 0.1. Amino acid metabolism (male and female pups) and phospholipid metabolism (male pups) were perturbed for the brain. Amino acid metabolism, purine metabolism, and TCA cycle were perturbed for tests and uterus. This study demonstrated the use of metabolomics to reveal metabolic perturbations in tissues of offspring following in utero exposures, and suggests the use of this approach for determining the impact of exposure past the time of the presence of the parent compound and metabolites derived from the parent compound.  相似文献   

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