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1.
目的 调查常见的环境激素在女童性早熟的发病机制中可能起到的作用,为阜阳地区儿童环境激素的暴露情况积累基础数据。方法 随机选取2020年10月—2021年4月在阜阳市人民医院生长发育专科门诊就诊的初诊为性早熟的女童,包括中枢性(CPP组)、外周性(PPP组)性早熟各30例,以及23例健康女童(正常对照组)作为研究对象,并就日常生活中可能接触到环境激素的途径填写相关内容调查问卷。应用超高效液相色谱串联质谱法测定3组女童尿液中15种环境激素的暴露水平,以及测定CPP组及PPP组女童的血清基础性激素、甲状腺激素水平,并完善性腺彩超等检查,进行3组女童尿液中环境激素暴露水平研究及相关性分析。结果 正常组、CPP及PPP 3组女童在使用塑料水杯方面、尿液中邻苯二甲酸单乙基己酯(MEHP)、邻苯二甲酸单丁基酯(MBP)的暴露水平分布差异具有统计学意义(χ2=8.111,F=3.741、5.672,P<0.05);CPP组与正常组女童尿MEHP、MBP暴露水平差异无统计学意义(P>0.05),但PPP与CPP组、PPP与正常组女童的尿MEHP、MBP暴露水平分布差异有统计学意义(P<0.05);PPP组内MEHP的分布水平与E2呈正相关关系(r=0.688,P<0.05)。结论 频繁使用塑料制品可能促进性早熟的发病;安徽阜阳地区女童普遍受到环境激素的污染;邻苯二甲酸单乙基己酯、邻苯二甲酸单丁基酯的暴露可能在外周性性早熟的病因中发挥着重要的作用,并且干扰体内性激素的分泌。  相似文献   
2.
Phthalates are found in different plastic materials, such as packaging, toys and medical devices. Some of these compounds are endocrine disruptors, comprising substances that are able to induce multiple hormonal disturbances and downstream developmental effects, including the disruption of androgen‐dependent differentiation of the male reproductive tract and changes in pathways that regulate hormone‐dependent behaviours. In a previous study, metabolites of diisopentyl phthalate (DiPeP), a potent anti‐androgenic phthalate, were found in the urine of Brazilian pregnant women. Therefore, the present study aimed to evaluate the effects of DiPeP exposure during critical developmental periods on behaviours controlled by sex hormones in rats. Pregnant Wistar rats were treated with DiPeP (1, 10 or 100 mg kg day‐1) or canola oil by oral gavage between gestational day 10 and post‐natal day (PND) 21. Male offspring were tested in a behavioural battery, including the elevated plus maze task, play behaviour, partner preference and sexual behaviour. After the behavioural tests, the hypothalamus and pituitary of these animals were removed on PND 60‐65 and PND 145‐160 to quantify gene expression for aromatase, androgen receptor (Ar) and oestrogen receptors α (Esr1) and β (Esr2). Male rats exposed to 1 and 10 mg kg day‐1 DiPeP displayed no preference for the female stimulus rat in the partner preference test and 1 mg kg day‐1 DiPeP rats also showed a significant increase in mount and penetration latencies when mated with receptive females. A decrease in pituitary Esr1 expression was observed in all DiPeP treated groups regardless of age. A reduction in hypothalamic Esr1 expression in rats exposed to 10 mg kg day‐1 DiPeP was also observed. No significant changes were found with respect to Ar, Esr2 and aromatase expression in the hypothalamus. These results suggest that DiPeP exposure during critical windows of development in rats may induce changes in behaviours related to mating and the sexual motivation of males.  相似文献   
3.
目的:探讨塑化剂邻苯二甲酸二(2-乙基己)酯(DEHP)对雌性大鼠子宫组织的影响,阐明DEHP对雌性大鼠子宫毒性作用的机制。方法:将48只成年雌性Wistar大鼠随机分为对照组(给予玉米油)、低剂量DEHP组(300 mg·kg-1·d-1DEHP,1/100 LD50)、中剂量DEHP组(1 000 mg·kg-1·d-1DEHP,1/30 LD50)和高剂量DEHP组(3 000 mg·kg-1·d-1DEHP,1/10 LD50),每组12只。于动情间期处死大鼠,称体质量,计算子宫脏器系数;HE染色法观察各组大鼠子宫组织病理形态表现;免疫组织化学染色法测定各组大鼠子宫组织中卵泡刺激素受体(FSHR)和黄体生成素受体(LHR)表达水平。结果:染毒第2、3、4周,各剂量DEHP组大鼠体质量低于对照组(P<0.05),且呈现明显的剂量-效应关系;各组大鼠子宫脏器系数比较差异无统计学意义(P>0.05)。肉眼可见对照组大鼠子宫形态正常,中和高剂量DEHP组大鼠子宫扭曲、管壁变薄,管腔内有大量黄色或清亮液体,并呈重度扩张;子宫浆膜面可见不同程度的积水、充血和肿胀现象。镜下各剂量DEHP组大鼠子宫内膜出现胞核假复层现象,上皮增生和内皮纤维化,固有层腺体数减少,部分腺体萎缩。与对照组比较,各剂量DEHP组大鼠子宫组织免疫组织化学染色程度逐渐减弱,面积减小。各剂量DEHP组大鼠子宫组织中FSHR表达水平比较差异无统计学意义(P>0.05)。与对照组比较,各剂量DEHP组大鼠子宫组织中LHR表达水平明显降低(P<0.05);且中和高剂量DEHP组大鼠明显低于低剂量DEHP组(P<0.05)。结论:DEHP可导致雌性大鼠体质量降低,子宫组织发生病理学改变,对雌性大鼠产生子宫毒性作用。  相似文献   
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The purpose of present study was to investigate the impact of butyl benzyl phthalate (BBP) on SH‐SY5Y neuroblastoma cells in vitro. The cell counting kit‐8 was used to measure cell proliferation and flow cytometry was utilized to study cell cycle phases and apoptosis. Western blotting and quantitative real‐time polymerase chain reaction were used to detect levels of aromatase, estrogen receptors (ERs) and some apoptosis and cell cycle‐related genes. Results showed BBP‐stimulated SH‐SY5Y cells in a dose‐dependent manner and produced a reverted U‐shaped dose‐response curve. BBP at lower concentrations (0.01 and 0.1 μm ) significantly induced cell proliferation while inhibited cell growth at 300 μm . The promoting effect of estradiol could be entirely blocked by administration of ICI182 780, a pure antagonist of ERs, while the effect of BBP could be partly blocked. Additionally, we confirmed 0.1 μm BBP‐induced cell proliferation caused the arrest of cells in S phase and inhibited apoptosis, which might be partially explained by the decreased expression of p53, the increased expression of proliferating cell nuclear antigen, Bcl‐2 and cell cycle regulator cyclin‐D1, and the activation of aromatase. The addition of ICI182 780 had no effect on BBP‐induced ERβ mRNA expression, whereas ICI182 780 could effectively counteract the effect of estradiol. Moreover, pretreatment with ICI182 780 could block the induction of aromatase protein expression and activity by BBP, showing an involvement of ERs. Except for the ER pathway, these results showed there might be other pathways involved in promoting the effects of low‐level BBP on SH‐SY5Y cells, which require further investigation.  相似文献   
7.
Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate for the production of flexible polyvinyl chloride. Recent studies in humans reported a widespread DEHP exposure, raising concerns in infants whose metabolic and excretory systems are immature. DEHP is a potential endocrine-disrupting chemical, but the effects of postnatal DEHP exposure on neuronal development are unclear. The dentate gyrus (DG) is critical in the consolidation of information from short- to long-term memory, as well as spatial learning. We evaluated neurodevelopmental toxicity due to neonatal DEHP exposure by assessing neurogenesis in the DG. Newborn mice were orally administered DEHP from postnatal day (PND) 12 to 25. We performed immunostaining using neuronal markers at different stages to assess whether DEHP exposure affects neurons at specific differentiation stages at PND 26 and PND 110. We found that in mice, postnatal DEHP exposure led to a decrease in the number of Type-1, -2a, -2b, and -3 neural progenitor cells, as well as granule cells in the hippocampal DG at PND 26. Further, the results showed that neural progenitor cell proliferation and differentiation were also reduced in the hippocampal DG of the DEHP-exposed mice. However, no effect on memory and learning was observed. Overall, our results suggest that neurodevelopmental toxicity due to postnatal DEHP exposure might affect postnatal DG morphogenesis.  相似文献   
8.
目的 探讨邻苯二甲酸二乙基己酯(DEHP)对小鼠焦虑样行为和学习记忆能力的影响及机制。方法 将40只雄性ICR小鼠随机分为对照组(0 mg/kg)和DEHP暴露组(10、50、100 mg/kg)。通过灌胃暴露DEHP 4周,再进行开场实验、高架十字迷宫实验和Morris水迷宫实验。取小鼠海马组织检测丙二醛(MDA)含量,取大脑进行HE切片观察海马组织形态学变化,检测海马组织紧密连接蛋白ZO-1、Occludin的分子表达。结果 与对照组相比,4周DEHP暴露对各组小鼠体质量未造成明显的影响(P>0.05)。行为学实验表明,DEHP暴露组小鼠在开场中心区域的运动距离(P<0.05)和停留时间(P<0.05)少于对照组;在高架十字迷宫开臂区的运动距离和停留时间少于对照组(P<0.05)。在Morris水迷宫实验中,和对照组小鼠相比,DEHP暴露组小鼠找到平台的潜伏期明显延长(P<0.05),且穿越平台位置的次数减少(P<0.05)。HE染色可以观察到海马CA1至CA3区出现明显的椎体细胞坏死,海马组织中MDA含量增加(P<0.05),且与血脑屏障完整性相关的ZO-1和Occludin在基因(P<0.01)、蛋白(P<0.05)水平的表达也显著降低。此外,多元线性回归分析显示,DEHP诱导的小鼠焦虑样行为与学习记忆能力之间有密切的关联性。结论 DEHP暴露可能通过破坏血脑屏障,损伤海马椎体神经细胞,进而诱导小鼠焦虑样行为和学习记忆能力下降。  相似文献   
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Mono-2-ethylhexyl phthalate (MEHP) is a major bioactive metabolite in the widely used industrial plasticizer diethylhexyl phthalate (DEHP) that has been found to be toxic to the liver. The aim of this study is to determine whether MEHP exposure can change the expression of fatty acid metabolism-related genes in HepG2 cells, which might be related to non-alcoholic fatty liver disease (NAFLD). The results revealed that exposure to MEHP promoted lipid accumulation in HepG2 cells. The levels of intracellular triglycerides in the hepatocytes increased after exposure to 0.8–100 μM MEHP for 24 h and 48 h. The genetic expressions of SREBP-1c, ChREBP, ACC1, FASN, and SCD significantly increased at 6 h after exposure to MEHP. At 24 h, the expression of the SREBP-1c and ChREBP genes remained increased, while the expression of the FASN and SCD genes decreased. At 48 h, the expression of SREBP-1c, ChREBP, ACC1, FASN, and SCD decreased. Furthermore, the levels of proteins including ACC1, FASN, SCD, and ChREBP (except SREBP-1c) increased at 24 h. These findings suggest that MEHP exposure can promote fatty acid synthesis in hepatocytes by regulating the expression of relevant genes and proteins, contributing to NAFLD.  相似文献   
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