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1.
Recently, developmental exposure to clothianidin (CLO) has been shown to cause reproductive toxicity in male mice, but the effects in female mice remain to be clarified. Pregnant C57BL/6N mice were given a no-observed-adverse-effect-level (NOAEL) dose of CLO until weaning. We then examined ovaries of 3- or 10-week-old female offspring. In the CLO-administered group, morphological changes, a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 (GPx4), and activation of genes in the steroid hormone biosynthesis pathway were observed in 3-week-old mice, and decreases of GPx4 immunoreactivity, 17OH-progesterone and corticosterone levels were observed in 10-week-old mice, along with high rates of infanticide and severe neglect, providing new evidence that developmental exposure to CLO affects juvenile and adult mice differently.  相似文献   

2.
Neonicotinoid pesticides (NNs) cause behavioral abnormalities in mammals, raising concerns about their effects on neural circuit activity. We herein examined the neurological effects of the NN clothianidin (CLO) by in vivo Ca2+ imaging using two-photon microscopy. Mice were fed the no-observed-adverse-effect-level (NOAEL) dose of CLO for 2 weeks and their neuronal activity in the primary somatosensory cortex (S1) was observed weekly for 2 weeks. CLO exposure caused a sustained influx of Ca2+ in neurons in the S1 2/3 layers, indicating hyperactivation of neurons. In addition, microarray gene expression analysis suggested the induction of neuroinflammation and changes in synaptic activity. These results demonstrate that exposure to the NOAEL dose of CLO can overactivate neurons and disrupt neuronal homeostasis.  相似文献   

3.
Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.  相似文献   

4.
Placental and breastfeeding transfer of soy isoflavones are potential routes for animal and human exposure to phytoestrogens, and reproductive dysfunctions have been linked to early exposure to these compounds. So, the aim of this study was to investigate the effects of perinatal (intrauterine and lactational) exposure to soy‐containing diet and soy‐derived isoflavones on the reproductive parameters of male rabbits. For this purpose, 12 female rabbits were randomly assigned to receive: (1) a soy‐ and alfalfa‐free diet (control diet); (2) a soy‐ and alfalfa‐free diet supplemented with 10 mg/kg body wt/day of soy isoflavones; (3) a soy‐ and alfalfa‐free diet supplemented with 20 mg/kg body wt/day of soy isoflavones; and (4) a diet containing 18% of soy meal, throughout gestation and lactation. Weight and morphology of the reproductive organs of some of the male offspring were evaluated at weaning (between days 29 and 31). The remaining males were placed on the control diet from weaning to adulthood (gestational and lactational exposure only). Sexual behaviour, semen quality and reproductive organs’ morphology were evaluated after puberty. There were no significant differences in litter size and gestation duration between control and treatment groups. Perinatal exposure to soy‐containing diet and soy isoflavones did not alter testis, epididymides, proprostate and prostate weight and gross morphology. After puberty, sexual behaviour and semen parameters did not differ significantly from the control group. These results indicate that intrauterine and lactational exposure to soy‐containing diet and soy‐derived isoflavones may not adversely affect reproductive development and function of male rabbits.  相似文献   

5.
本试验旨在探究肌肉生长抑制素（myostatin，MSTN）基因在小鼠不同发育阶段心肌组织中的表达情况，分别选取幼年（7日龄）、性成熟（21~28日龄）、体成熟（42~56日龄）和老年（84日龄以上）4个发育阶段的健康小鼠（各3只）为研究对象，采用实时荧光定量PCR、HE染色、免疫组织化学等方法研究小鼠不同发育时期MSTN基因在心肌组织中的表达及不同时期心肌组织的发育。实时荧光定量PCR结果显示，MSTN基因在小鼠不同发育阶段心肌组织中均有表达，且其在小鼠老年时期的表达量最高，体成熟时期的表达量最低；幼年小鼠和性成熟小鼠心肌组织中MSTN基因表达水平显著低于老年小鼠（P<0.05），而体成熟小鼠则极显著性低于老年小鼠（P<0.01）。HE染色结果显示，小鼠心肌细胞核及肌纤维的生长在不同发育时期明显不同，其中幼年时期的细胞核最多，肌纤维排列相对较紧密，而在性成熟、体成熟、老年时期心肌的发育指标依次降低。免疫组织化学结果显示，MSTN基因主要在心肌细胞核中表达，其各个时期表达量与实时荧光定量PCR的结果相符合。  相似文献   

6.
Bisphenol A (BPA), a ubiquitous environmental contaminant, has been shown to cause developmental toxicity and carcinogenic effects. BPA may have physiological activity through estrogen receptor (ER) -α and -β, which are expressed in the central nervous system. We previously found that exposure of BPA to immature mice resulted in behavioral alternation, suggesting that overexposure of BPA could be neurotoxic. In this study, we further investigated the molecular neurotoxic mechanisms of BPA. BPA increased vulnerability (decrease of cell viability and differentiation, and increase of apoptotic cell death) of undifferentiated PC12 cells and cortical neuronal cells isolated from gestation 18 day rat embryos in a concentration-dependent manner (more than 50 µM). The ER antagonists, ICI 182,780, and tamoxifen, did not block these effects. The cell vulnerability against BPA was not significantly different in the PC12 cells overexpressing ER-α and ER-β compared with PC12 cells expressing vector alone. In addition, there was no difference observed between BPA and 17-β estradiol, a well-known agonist of ER receptor in the induction of neurotoxic responses. Further study of the mechanism showed that BPA significantly activated extracellular signal-regulated kinase (ERK) but inhibited anti-apoptotic nuclear factor kappa B (NF-κB) activation. In addition, ERK-specific inhibitor, PD 98,059, reversed BPA-induced cell death and restored NF-κB activity. This study demonstrated that exposure to BPA can cause neuronal cell death which may eventually be related with behavioral alternation in vivo. However, this neurotoxic effect may not be directly mediated through an ER receptor, as an ERK/NF-κB pathway may be more closely involved in BPA-induced neuronal toxicity.  相似文献   

7.
Lymphopoiesis in fetal thymuses of mice and rabbits was studied to try to correlate heterogeneity of lymphocytes with heterogeneity of embryonic origin. The thymuses of fetal mice of 11 to 14 days gestation and of fetal rabbits of 18 and 19 days gestation were examined by electron microscopy. At the time of earliest appearance of lymphoid cells in both species desmosomes were seen on both epithelial and lymphoid cells. These desmosomes persisted for several days, then disappeared from completely differentiated lymphocytes in both species. The similarity between epithelial and lymphoid cells in their earliest developmental stages suggests a common precursor cell for both.  相似文献   

8.
To identify clones that corresponded to developmentally regulated genes in pig liver, recombinant cDNA libraries were constructed from early fetal (d 40), late fetal (d 110) and adult liver mRNA. Each library was screened by probing with total cDNA prepared from mRNA at different stages of development. Nine clones that gave distinct developmental patterns when hybridized to liver RNA isolated from various stages of development were subsequently isolated and partially sequenced. The cognate proteins for seven of these clones were identified by searching a national DNA sequence resource (Bionet) for similar sequences. Clones hybridizing to mRNA that was most abundant early in development were alpha fetoprotein, alpha 1 antiprotease, alpha globin and an unidentified clone. The mRNA for beta and gamma fibrinogen were most abundant perinatally. The abundance of mRNA for albumin, haptoglobin and a second unidentified clone was low in fetal liver, but increased to adult levels between birth and 3 d of age. These clones provide probes to study the relationship between factors affecting fetal growth and expression of specific genes throughout the development.  相似文献   

9.
It is known that topical all-trans-retinoic acid (RA) modulates growth and differentiation of skin and its cutaneous appendages. To examine whether a pre-natal exposure to a potentially non-teratogenic dosage of all-trans-RA had any effect on vibrissal follicle development, the histologic and immunohistochemical responses to RA during its morphogenesis in NMRI mouse were investigated. After a single oral dose of 30 mg/kg body weight of all-trans-RA on day 11.5 of gestation, no fetal malformations were detected and the histological features and the distribution of keratin (K) proteins in comparable stages of vibrissal development were similar for the untreated, vehicle-treated and RA-treated mice. The absence of teratogenic response and of adverse effects on the vibrissae under the experimental conditions indicates that this protocol may be useful for investigation of the effects of pre-natal exposure to RA on the post-natal development of experimental tumours in the mouse skin.  相似文献   

10.
Although our previous report demonstrated that adiponectin and AdipoR1 gene expressions changed among different lactation stages in the bovine mammary gland, its in vivo kinetics remain unclear in ruminant animals. In this study, we investigated the changes in circulating concentrations of adiponectin, as well as other metabolic hormones and metabolites, (i) during the periparturient period and (ii) among different lactation stages, in Holstein dairy cows. In experiment 1, serum adiponectin concentrations increased after parturition. Serum insulin concentrations were lower in the postpartum than prepartum period, whereas serum growth hormone (GH) concentrations increased in the postpartum period. Serum nonesterified fatty acids (NEFA) levels were increased during the postpartum period and were dependent on the parity. In experiment 2, there was no significant difference in plasma adiponectin concentrations among lactational stages. Plasma insulin concentrations tended to be lower in early lactation while plasma GH levels tended to be higher. Plasma NEFA concentrations were significantly lower in mid‐ and late‐lactation stages than non‐lactation stages. These findings indicate that elevation of serum adiponectin might be involved in energy metabolism just around parturition, and might exert its action through regulation of receptor expression levels in target tissues in each lactational stage in Holstein dairy cows.  相似文献   

11.
试验旨在研究氧化应激对子代小鼠产生的影响。对亲代的公鼠和母鼠分别腹腔注射12.5 μg/g三硝基丙酸（3-NPA），分为正常公鼠与正常母鼠交配的对照组（C）、正常公鼠与3-NPA处理的母鼠交配组（FM）、正常母鼠与3-NPA处理的公鼠交配组（MM）、3-NPA处理的公鼠与3-NPA处理的母鼠交配组（DM）共4组，试验重复3次。通过剖出胎鼠的方法统计子代胎鼠的数量，采集子代胎鼠的心脏、肝脏、肺脏3个器官，测定超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-PX）的活力及总抗氧化能力（T-AOC）。结果显示，与对照组相比，FM组胎鼠数量下降不明显（P>0.05），MM和DM组胎鼠数量均显著减少（P<0.05）；FM与DM组胎鼠肝脏、肺脏中CAT活力均显著增加（P<0.05）；MM组胎鼠肝脏、肺脏中CAT活力增加，但差异不显著（P>0.05）；各组心脏中CAT活力均增加，但差异均不显著（P>0.05）；除MM组肺脏中T-AOC活力增加差异不显著（P>0.05），其余各组肝脏、肺脏和心脏中T-AOC活力均显著增加（P<0.05）；DM组胎鼠肝脏中GSH-Px活力显著增加（P<0.05），FM和MM组胎鼠肝脏中GSH-Px活力增加，但差异不显著（P>0.05）；FM与DM组胎鼠肺脏中GSH-Px活力显著升高（P<0.05）；各组心脏中GSH-Px活力均差异不显著（P>0.05）；DM组胎鼠肝脏、肺脏、心脏中SOD活力均显著增加（P<0.05），FM和MM组胎鼠肝脏、肺脏、心脏中SOD活力增加，但差异均不显著（P>0.05）。因此，试验成功构建3-NPA氧化应激小鼠模型，且亲代雄性小鼠氧化应激对胎鼠影响较大。  相似文献   

12.
This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.  相似文献   

13.
Serum alkaline phosphatase (ALP) activities were measured during dry and lactational periods to investigate the influence of lactation on serum ALP activity in cows. Higher levels of serum ALP activity were seen in lactational periods than in dry periods. The serum activities of bone-specific ALP (BALP), liver ALP (LALP), tartrate resistant acid phosphatase (TRAP) and aspartate aminotransferase also increased in lactational periods. ALP activities in the bone extract and in whey were decreased at similar rates by the addition of lectin. Moreover, since the ALP band in whey was observed to have the same migration in polyacrylamide gel (PAG) disk electrophoresis as that of the bone extract, analysis of ALP isoenzymes by lectin affinity or PAG disk electrophoresis could not distinguish ALP originating from the mammary gland from that of bone. In this study, it was clear that the increased level of serum ALP activity was due to increases of BALP and LALP in lactational periods. However, the extent of the influence of ALP originating from the mammary glands on serum ALP activity was unknown. Judging from changes of BALP and TRAP activities in the serum and the correlation between the both, it was guessed that ALP originating from the mammary glands influenced serum ALP activity.  相似文献   

14.
Ovaries of unilaterally ovulated goats (n=21) were used to study follicular morphological features (proportion and degree of atresia, oestradiol production in vitro and progesterone production of granulosa cells in culture). Follicles were dissected out and classified as small (1–2 mm), medium (2–4 mm) and large (>4 mm). Morphological and physiological features were compared in each size class between ovaries bearing and not bearing corpora lutea (CLO and NCLO, respectively). Within the same size class, there was no difference in proportion or in degree of atresia, between CLO and NCLO. A significant effect of follicular size on oestradiol production in vitro was detected, but no effect of the corpus luteum was found. Finally, progesterone production of granulosa cells in culture was significantly higher in CLO than in NCLO after 24 h (p < 0.05) and also after 90 h (p < 0.01) of culture. This higher progesterone production by CLO granulosa cells in culture could be explained by local influence of the corpus luteum stimulating the steroidogenic activity but not aromatase activity. Further studies are needed to clarify possible factors and pathways for this local effect of the corpus luteum upon follicular physiology.  相似文献   

15.
This study investigated the effects of intravenous (IV) administration of tetrathiomolybdate (TTM), and α(2)-adrenergic agonist clonidine (CLO) and α(2)-antagonist idazoxan (IDA), alone or in combination with TTM, on sheep fed low (LCu) and high (HCu) copper diets. Effects on bile flow, biliary Cu concentration and excretion, plasma Cu concentration, and lysosomal enzyme β-glucuronidase (β-GLU) activity in bile and plasma were determined. Tetrathiomolybdate alone or with CLO or IDA significantly enhanced biliary Cu excretion most likely by removing Cu from hepatocyte lysosomes as evidenced by a significant increase in β-GLU enzyme activity in bile. A significant increase in plasma β-GLU concentration occurred only in sheep treated with CLO in combination with TTM. Because of the lytic nature of the lysosomal enzymes, caution is advocated in use of drugs, especially α(2)-adrenergic agonists, to further enhance TTM-induced biliary Cu excretion in the treatment of chronic Cu poisoning in sheep.  相似文献   

16.
Impaired wound healing is an important problem; retardation of healing may be induced by endogenous and/or exogenous factors and treatments capable of ameliorating these effects are needed. The effects of solutions containing light ichthyol or povidone iodine, of ointments containing zinc oxide (ZO) and/or cod liver oil (CLO), and of a polyurethane-hydrogel foam wound dressing were examined on healing of full-thickness murine skin wounds impaired by systemic dexamethasone. The effects of the ointments were also studied on murine skin ulceration induced by subcutaneous sodium dodecyl sulphate solution. Light ichthyol at 1% and 2% but not at 5% and 10%, povidone iodine at 1% and the foam accelerated impaired healing. The ointments containing ZO or CLO accelerated healing of impaired full-thickness wounds and of ulcerated skin; ZO and CLO were synergistic. These studies demonstrate the value of murine models in the evaluation of agents employed in veterinary wound dressings.  相似文献   

17.
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18.
The appropriate literature has been reviewed for the purpose of defining the phenomenon of stress in lactating dairy cattle, establishing a baseline concept of lactation stress and emphasizing the most significant aspects of the natural mammary defence mechanisms. Data on the general adaptation syndrome (GAS) make it clear that stress is essentially the rate of wear and tear of the biological system affected by a stressor either eliciting stress of the organism as a whole or partly so. Owing to the variety of stressors which may affect the dairy cow at physiological and pathological levels, a definition of stress in the broad sense is indicated. This is essential from the point of view of the anti-homeostatic effects (metabolic and immunological) of lactation stress, aggravated by anti-homeostatic effects elicited by superimposed other types of stress (e.g. heat stress). The lactating cow, as a ruminant in a state of sustained stress, requires a special profile of hormonal mediators. In high yielding cows, for example, acute and sustained heat stress promotes increased activities of prolactin, progesterone and catecholamines. Compared with the mainly glycogenic/glycogenolytic metabolism of non-ruminant mammals, the lipogenic/lipolytic and glycogenic/glycogenolytic metabolism of the dairy cow depends on hormonal mediators which differ from those of the former not so much in their nature but in their magnitude and ratios. Stressors induce the development of GAS reactions in the dairy cow. These enable the cow to create and maintain homeostasis of its integrated 3 main physio-pathological systems and thus to endure the stressor(s). The cow's compensating adjustments to a stressor are therefore the effects of stress. This means that natural lactation is the effect of the lactation stress induced by the cow's progeny (i.e. the natural lactation stressor). Artificial lactation stressors (e.g. removal of milk by hand and machine) may affect the lactation stress in magnitude but not necessarily in nature. Likewise, a range of behavioural, physiological, lactational and lacteal changes related to other stressors are the effects of different types of stress. Lactation stress, like other types of stress, shows 3 stages of development, i.e., an overcompensating alarm phase (= lactogenesis), resistance phase (= galactopoiesis) and exhaustion phase (= regression). They facilitate adjustments of the cow's homeostasis from the level of involutional homeostasis (= no lactational activity) to that of lactational homeostasis. Like other tissues in a state of stress, the lactating mammary epithelium requires a greatly increased supply of glucose.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

19.
应用旷场试验测定不同时长4℃冷暴露下采食和禁食C57BL/6小鼠的自发运动,并结合骨骼肌中PGC-lα与ERRα表达水平,探讨低温环境下禁食对C57BL/6小鼠自发运动的影响。结果显示,低温环境下禁食对C57BL/6小鼠的自发运动并无显著性影响,但焦虑情绪12 h差异显著(P<0.05),探索行为8 h和12 h差异极显著(P<0.01);腓肠肌中PGC-1α表达在4,8 h时差异极显著(P<0.01),12 h差异显著(P<0.05);ERRα表达在4,6 h时差异极显著(P<0.01)。结果表明,低温环境下禁食对C57BL/6小鼠自发运动未出现明显影响,而对小鼠焦虑情绪、探索行为和腓肠肌中PGC-lα、ERRα表达存在不同程度的影响,相比于禁食而言,冷刺激对小鼠机体的影响更大。  相似文献   

20.
The objective of this study was to characterize the effect of dose and type of cloprostenol (CLO) on the luteolytic response of dairy cattle during the Ovsynch protocol under different oestrus cycle and physiological characteristics. Twelve non‐lactating dairy cows and 111 lactating dairy cows were used in three experiments. In Experiment I, cows were synchronized so that they had only a 5.5‐ to 6‐day‐old corpus luteum (CL) at the time of the prostaglandin F2α (PGF2α) treatment of Ovsynch. In Experiment II, cows were synchronized so that they had at least a CL of approximately 14 days old at the time of PGF2α treatment and an accessory CL if they had responded to the first GnRH of Ovsynch. Furthermore, in each experiment, cows received either a standard or a double dose of d‐CLO as the luteolytic treatment. In Experiment III, lactating cows were blocked by parity and assigned to one of three luteolytic treatments during Ovsynch: 500 μg d,l‐CLO, 150 or 300 μg of d‐CLO. In Experiment I, the dose of d‐CLO had an effect (p = 0.08) on the percentage of cows with full luteolysis, but not in Experiment II (p > 0.1). More cows in Experiment II had full luteolysis than did cows of Experiment I (87% vs 58%, respectively; p = 0.007). In Experiment III, 87.1%, 84.4% and 86.2% lactating dairy cows had full luteolysis and 37.8%, 36.8% and 36.1% of cows became pregnant after treatment with 500 μg d,l‐CLO, 150 or 300 μg of d‐CLO, respectively (p > 0.05).  相似文献   

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