Green tea polyphenols alleviate di-(2-ethylhexyl)phthalate-induced liver injury in mice

BACKGROUND Di(2-ethylhexyl)phthalate(DEHP)is a common plasticizer known to cause liver injury.Green tea is reported to exert therapeutic effects on heavy metal exposureinduced organ damage.However,limited studies have examined the therapeutic effects of green tea polyphenols(GTPs)on DEHP-induced liver damage.AIM To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage.METHODS C57BL/6J mice were divided into the following five groups:Control,model[DEHP(1500 mg/kg bodyweight)],treatment[DEHP(1500 mg/kg bodyweight)+GTP(70 mg/kg bodyweight),oil,and GTP(70 mg/kg bodyweight)]groups.After 8 wk,the liver function,blood lipid profile,and liver histopathology were examined.Differentially expressed micro RNAs(miRNAs)and mRNAs in the liver tissues were examined using high-throughput sequencing.Additionally,functional enrichment analysis and immune infiltration prediction were performed.The miRNA-mRNA regulatory axis was elucidated using the starBase database.Protein expression was evaluated using immunohistochemistry.RESULTS GTPs alleviated DHEP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,liver fibrosis,and mitochondrial and endoplasmic reticulum lesions in mice.The infiltration of macrophages,mast cells,and natural killer cells varied between the model and treatment groups.mmu-miR-141-3p(a differentially expressed miRNA),Zcchc24(a differentially expressed mRNA),and Zcchc24(a differentially expressed protein)constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice.CONCLUSION This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,and partial liver fibrosis,and regulate immune cell infiltration.Additionally,an important miRNAmRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.

Di-(n-butyl)-phthalate-induced Oxidative Stress and Depression-like Behavior in Mice with or without Ovalbumin Immunization

Objective To investigate the relationship between atopic allergy and depression and the role of DBP in the development of depression. Methods BALB/c mice were randomly divided into eight groups：saline;ovalbumin （OVA）-immunized;saline＋DBP （0.45 mg/kg·183;d）; saline＋DBP （45 mg/kg·d）; DBP （0.45 mg/kg·d） OVA-immunized; DBP （45 mg/kg·d） OVA-immunized; saline＋hydrocortisone （30 mg/kg·d）; and hydrocortisone （30 mg/kg·d）-exposed OVA-immunized. Behavior （e.g. open-field, tail suspension, and forced swimming tests）, viscera coefficients （brain and spleen）, oxidative damage [e.g. reactive oxygen species （ROS）, malondialdehyde （MDA）, and glutathione （GSH）], as well as levels of IgE and IL-4, were then analyzed. Results In the saline and OVA groups, the degree of depression symptoms in mice increased with increasing DBP concentration. Additionally, the OVA-immunity groups were associated with more serious depressive behavior compared with the same exposure concentration in the saline group. Oxidative damage was associated with a dose-dependent increase in DBP in the different groups. IL-4 and IgE levels were associated with low-dose DBP stimulation, which changed to high-dose inhibition with increasing DBP exposure, possibly due to spleen injury seen at high DBP concentrations.Conclusion Development of an atopic allergy has the potential to increase the risk of depression in mice, and it seems that DBP helps OVA to exert its effect in our present model. Moreover, the results of our study implicate a certain connection between brain oxidative stress and depression, which deserves a further exploration.

Developmental Toxicity in Mice Following Paternal Exposure to Di-N-Butyl-Phthalate (DBP)

Objective The aim of the present study was to investigate the effects of paternal Di‐N‐butyl‐phthalate （DBP） exposure pre‐ and postnatally on F1 generation offspring,and prenatally on F2 generation offspring.Methods Male mice were exposed to either 500 mg/kg or 2 000 mg/kg of DBP for 8 weeks,and mated with non‐exposed females.Three‐quarters of the females were sacrificed a day prior to parturition,and examined for the number of living and dead implantations,and incidence of gross malformations.Pups from the remaining females were assessed for developmental markers,growth parameters,as well as sperm quantity and quality.Results There were no changes in the fertility of parents and in intrauterine development of the offspring.Pups of DBP‐exposed males demonstrated growth‐retardation.Following paternal exposure to 500 mg/kg bw of DBP,there were almost twice the number of males than females born in the F1 generation.F1 generation females had a 2.5‐day delay in vaginal opening.Paternal exposure to 2 000 mg/kg bw of DBP increased the incidence of sperm head malformations in F1 generation males;however,there were no changes in the fertility and viability of foetuses in the F2 generation.Conclusion Paternal DBP exposure may disturb the sex ratio of the offspring,delay female sexual maturation,and deteriorate the sperm quality of F1 generation males.

Effects of di-n-butyl phthalate on male rat reproduction following pubertal exposure

Di-n-butyl phthalate （DBP） is an endocrine-disrupting chemical that has the potential to affect male reproduction. However, the reproductive effects of low-dose DBP are still not well known, especially at the molecular level. In the present study, pubertal male Sprague-Dawley rats were orally administered DBP at a wide range of doses （0.1, 1.0, 10, 100 and 500 mg kg^-1 day^-1） for 30 days. The selected end points included reproductive organ weights, testicular histopathology and serum hormonal levels. Additionally, proteomic analysis was performed to identify proteins that are differentially expressed as a result of exposure to DBP at low doses （0.1, 1.0 and 10 mg kg^-1 day^-1）. Toxic effects were observed in the high-dose groups, including anomalous development of testes and epididymides, severe atrophy of seminiferous tubules, loss of spermatogenesis and abnormal levels of serum hormones. Treatment with low doses of DBP seemed to exert a ＇stimulative effect＇ on the serum hormones. Proteomics analysis of rat testes showed 20 differentially expressed proteins. Among these proteins, alterations in the expression of HnRNPA2/B1, vimentin and superoxide dismutase 1 （SOD1） were further confirmed by Western blot and immunohistochemistry. Taken together, we conclude that high doses of DBP led to testicular toxicity, and low doses of DBP led to changes in the expression of proteins involved in spermatogenesis as well as changes in the number and function of Sertoli and Leydig cells, although no obvious morphological changes appeared. The identification of these differentially expressed proteins provides important information about the mechanisms underlying the effects of DBP on male rat reproduction.

Removal of a type of endocrine disruptors—di-n-butyl phthalate from water by ozonation

Ozonation of synthetic water containing a type of endocrine disruptor-di-n-butyl phthalate （DBP） was examined. Key impact factors such as pH, temperature, ionic strength, ozone dosage and initial DBP concentration were investigated. In addition, the activities of radicals on uncatalysed and catalysed ozonation were studied. The degradation intermediate products were followed and the kinetic of the ozonation were assessed as well. Results revealed that ozonation of DBP followed two mechanisms. Firstly, the reaction rate of direct ozonation was slower at lower pH, temperature, and ionic strength. Secondly, when these factors were increased for indirect radical reaction, higher percentage of DBP was removed with the increase of the initial ozone dosage and the decrease of the initial DBP concentration. In addition, tea-butanol, humic substances and Fe（Ⅱ） affected DBP ozonation through the radical pathway. It was determined that ozonation was restrained by adding tea-butanol for its radical inhibition effect. Furthermore, humic substances enhanced the reaction to some extent, but a slight negative effect would be encountered if the optimum dosage was exceeded. As a matter of fact, Mn（Ⅱ） affected the ozonation by ＂active sites＂ mechanism. In the experiment, three different kinds of intermediate products were produced during ozonation, but the amount of products for each one of them decreased as pH, temperature, ionic strength and initial ozone dosage increased. A kinetic equation of the reaction between ozone and DBP was obtained.

Aerobic biodegradation of di-n-butyl phthalate by Xiangjiang River sediment and microflora analysis

Di-n-butyl phthalate (DBP),one of phthalate acid esters (PAEs),was investigated to determine its biodegradation rate using Xiangjiang River sediment and find potential DBP degraders in the enrichment culture of the sediment. The sediment sample was incubated with an initial concentration of DBP of 100 mg/L for 5 d. The biodegradation rate of DBP was detected using HPLC and the degraded products were analyzed by GC/MS. Subsequently,the microbial diversity of the enrichment culture was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results reveal that almost 100% of DBP is degraded after merely 3 d,generating two main degraded products:mono-butyl phthalate (MBP) and 9-octadecenoic acid. After a six-month enrichment period under the pressure of DBP,the dominant family in the final enrichment culture is clustered with the Comamonas sp.,the remaining are affiliated with Sphingomonas sp.,Hydrogenophaga sp.,Rhizobium sp.,and Acidovorax sp. The results show the potential of these bacteria to be used in the bioremediation of DBP in the environment.

Vapor Pressures of Di-n-Butyl Phthalate and Di-iso-Butyl Hexahydrophthalate at Reduced Pressures

In this paper the measured values of the vapor pressures by ebulliometer method of two important maleic anhydride recovery solvents, di-n-butyl phthalate (DBP) and di-iso-butyl hexahydrophthalate (DIBE), between 0.63—17.79 kPa and 0.49—30.95 kPa,are reported respectively.A comparison of the data of DBP with the published data has been made, which shows good consistency. For the convenient use of these vapor pressures, Cragoe equation, Antoine equation and Kirchhoff equation are selected to correlate them. The correlating results show that Antoine equation is the best one of the three equations to fit for the vapor pressures of the two solvents. According to Clausius-Clapeyron equation, the linear relationship between natural logarithm of pressure and reciprocal of temperature is used to calculate the molar latent heats of evaporation of the two organic solvents. The molar latent heats of evaporation of DBP and DIBE are 75.1 kJ/mol and 67.7 kJ/mol, respectively.

Glycerin Monostearate Aggravates Male Reproductive Toxicity Caused by Di(2-ethylhexyl)Phthalate in Rats

Human beings are increasingly exposed to phthalates,which are a group of chemicals used to make plastics more flexible and harder to break,and simultaneously ingesting abundant food emulsifiers via daily diet.The purpose of this study was to investigate the effect of the food emulsifier glycerin monostearate(GMS)on male reproductive toxicity caused by di(2-ethylhexyl)phthalate(DEHP,one of the phthalates)and explore the underlying mechanism.Thirty male Sprague-Dawley rats were randomly divided into control group,DEHP group and DEHP+GMS group.Rats in the DEHP group and DEHP+GMS group were orally administered with 200 mg/kg/d DEHP with or without 20 mg/kg/d GMS.After 30 days of continuous intervention,it was found that the serum testosterone level was significantly lowered in DEHP group and DEHP+GMS group than that in control group(P<0.01).The serum testosterone level and the relative testis weight were significantly decreased in the DEHP+GMS group as compared with those in the DEHP group and control group(P<0.05).More spermatids were observed to be shed off in DEHP+GMS group than in DEHP group.The expression levels of cell cycle checkpoint kinase 1(Chkl),cell division cycle gene 2(Cdc2),and cyclin-dependent kinase 2(CDK2)were down-regulated in DEHP group,and this tendency was more significant in DEHP+GMS group(P<0.05 or P<0.01).There was no significant difference in the P-glycoprotein(P-gp)expression between DEHP group and control group.However,P-gp was markedly down-regulated in DEHP+GMS group(P<O.Ol).The results indicated that the food emulsifier GMS aggravated the toxicity of DEHP on male reproduction by inhibiting the cell cycle of testicular cells and the expression of P-gp in testis tissues.

An Estimation of the Daily Intake of Di(2-ethlhexyl) Phthalate(DEHP) among Workers in Flavoring Factories

Objective To estimate the daily intake of DEHP among workers in flavoring factories. Methods 71 workers in two flavoring manufacturers, 27 administrators in those factories and 31 laboratory technicians in a research institute were recruited and assigned to exposure group, control group 1 and control group 2 respectively. Their urinary DEHP metabolites, mono（2-ethylhexyl） phthalate （MEHP）, mono-（2-ethyl-5-hydroxyhexyl） phthalate （MEHHP）, mono-（2-ethyl-5-oxohexyl） phthalate （MEOHP）, were detected by isotope dilution-ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）. The urinary metabolites concentrations were converted into DEHP intake levels using two pharmacokinetic models： the urine creatinine-excretion （UCE） one and the urine volume （UV） one. Results No significant differences were found among the three groups. Based on the urinary concentrations of Z3MEHP, we got a median daily DEHP intake of 3.22 or 1.85 μg/kg body-weight/day applying the UV or UCE models respectively. Depending on the UV model, three subjects （2.34%） exceeded the RfD value given by US EPA and the P50 of estimate daily DEHP intakes accounted for 16.10% of the RfD value. No subjects exceeded the limitation depending on the UCE model. Conclusion The workers in flavoring factories were not supposed to be the high DEHP exposure ones and their exposure level remained at a low risk.

Effects of Low Concentrations of Di-(2-ethylhexyl) and Mono-(2-ethylhexyl) Phthalate on Steroidogenesis Pathways and Apoptosis in the Murine Leydig Tumor Cell Line MLTC-1

The aim of this study was to evaluate the effects of low concentrations of DEHP and MEHP on steroidogenesis in a murine Leydig tumor cell line （MLTC-1） in vitro. The result of flow cytometry analysis revealed that the proportion of apoptotic cells was significantly increased after the exposure to DEHP. All three genes （P450scc, P450c17, and 38HSD） under study showed an increased expression following exposure to DEHP or MEHP, although some insignificant inhibitory effects appeared in the 10μmol/L treatment group as compared with the controls. It was also found that DEHP or MEHP stimulated INSL3 mRNA and protein especially in the 0.001 μmol/L treatment group. Testosterone secretions were stimulated after the exposure to DEHP or MEHP. Alterations of steroidogenic enzymes and INSL3 in MLTC-1 cells might be involved in the biphasic effects of DEHP/MEHP on androgen production.

Long-term effects of di-octyl phthalate on the expression of immune-related genes in Tegillarca granosa

Di-octyl phthalate(DOP) is widely used as a plasticizer in the plastics industry.As a result,DOP is often found in marine water ecosystems where many species are exposed to it.Our objective was to evaluate the effect of long-term(14 d) DOP exposure(2.6,7.8,or 31.2 mg/L) on the expression of immunerelated genes in Tegillarca granosa.The expression of small heat shock protein(sHSPs) and tissue inhibitor of metalloproteinase(TIMP) were highest in clams exposed to 31.2 mg/L DOP on days 7 and 14.The relative expression of Tg-ferritin,superoxide dismutase(SOD),and metallothionein(MT) increased initially then decreased as the concentration of DOP increased.The hemoglobin of T.granosa(Tg-Hb I) exhibited two distinct expression patterns at two time points.Our results suggest that the immune response of T.granosa against DOP pollution varies depending on the dose.Additionally,we identified some immune-related genes that are promising candidates for biomarkers of DOP.

Aquatic toxicity of di (2-eihylhexyl) phthalate to duckweeds

This study is concerned with the effects of di （2-ethylhexyl） phthalate （DEHP） on two kinds of duckweeds （Spirodela polyrhiza and Lemna minor）.The results indicate that DEHP has aquatic toxicity to Spirodela polyrhiza at 0.4 mg/L and to Lemna minor at over 0.1 mg/L by changing their physiologic-biochemical characteristics.The contents of duckweed chlorophyll and soluble protein decrease with increasing DEHP concentration after 7 d of exposure.DEHP shows the stimulating role in catalase （CAT） and superoxide dismutase （SOD） systems at relative low levels.At 0.01 mg/L and 0.005 mg/L,SOD activities of Spirodela polyrhiza and Lemna minor reach their peak values respectively,while CAT activity reaches its maximum value at 0.05 mg/L and 0.01 mg/L.When DEHP levels are too high,the protection enzyme system would be destroyed and plant growth is inhibited.The analysis of malondialdehyde （MDA） and Fourier transform infrared spectroscopy manifest that DEHP could affect the tested duckweeds by destroying its cell membranes,and Spirodela polyrhiza is more resistant to DEHP exposure than Lemna minor.

Impairment of Di(2-Ethylhexyl) Phthalate on Cellular Immunity in Kunming Mice

Immunity is crucial to the health of animals and it can determine their survival and fitness. Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer and hence is the most abundant phthalate in the environment. Exposure to DEHP is of great concern for human health. In the present study, we tested the hypothesis that exposure to DEHP would suppress T cell-mediated immunity in mice. Twenty adult male Kunming mice were randomly assigned into the control (n = 10) and the DEHP treatment (n = 10) groups. Both groups have free access to food and water, while the mice in the latter group drank DEHP solution (2000 mg/L) for 42 days. T cell-mediated immunity assessed by phytohaemagglutinin (PHA) response was depressed in the DEHP treated mice compared with the controls, however, wet thymus and spleen mass, white blood cells were not influenced by DEHP treatment. Taken together, different immunological parameters responded differently to DEHP treatment in Kunming mice.

The Development of Metabolic Derangement in Male Offspring after Perinatal Exposure to Di-(2-Ethylhexyl) Phthalate

The prevalence of obesity and type 2 diabetes mellitus（T2DM）has been increasing throughout the world over the past 20 years.Environmental chemicals known to regulate the endocrine system have been considered as a risk factor for the development of metabolic diseases.Several people are exposed to environmental chemicals during their lives.

Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate

Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.

Combined Effects of Dibutyl Phthalate (DBP) and Benzo(a)Pyrene on Fertility in Male Rats

Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the toxicity in male fertility when combined. Thus we used di-n-butyl phthalate (DBP) and Benzo(a)pyrene (Bap) as their representatives respectively to explore their effects on the spermatogenesis in male rats. Male Sprague Dawley rats were randomly divided into 4 groups and respectively exposed to corn oil, Bap (5 mg/kg/d), DBP (250 mg/kg/d), and combined doses of Bap (5 mg/kg/d) and DBP (250 mg/kg/d) for 90 days. We observed a significant increase in the stillbirth rate after Bap and combined treatments, while the mean area of seminiferous tubules was reduced after Bap, DBP and combined treatments. Bap and combined treatment had a sup- pressing effect on meiosis in germ cells, which reduced the haploid contents and the ratio between haploid and diploid but increased the tetraploid and diploid contents and the ratio between hap- loid and tetraploid. These effects were more obvious in the combined group. Furthermore, the ex- pression of a number of proteins was changed, of which was associated with the oxidative stress and cAMP/PKA signaling pathway. Our results suggest that Bap has significant toxic effects on male fertility, while the combined treatment of Bap and DBP has more toxic effects.

Reducing children’s exposure to di(2-ethylhexyl)phthalate in homes and kindergartens in China:Impact on lifetime cancer risks and burden of disease

Exposure to di(2-ethylhexyl)phthalate(DEHP)in the indoor environment has been linked with significant health risks for Chinese children.Multi-phase DEHP concentrations in Chinese residences and kindergartens were estimated using a mass balance model based on the current baseline condition and control strategies(i.e.,increasing ventilation rate,reducing area of sources,using mechanical ventilation systems,and using portable air cleaners).The health benefits of each control strategy were quantified as the reduction in lifetime cancer risks(LCR)and burden of disease(BoD).In the current situation,the mean LCR and disability-adjusted life years(DALY)number attributable to indoor DEHP exposure for Chinese children were around 6.0×10^(−6) and 155 thousand,respectively.The mean LCR and DALY might be reduced by 25%-54%and 16%-40%,respectively,by increasing air exchange rates by 100%,reducing the use of source materials by two-thirds or deploying commercial air cleaners in naturally ventilated buildings.Meanwhile,avoidable DALYs could result in a reduction of mean economic losses of 2.2-5.3 billion RMB.Mechanical ventilation systems with filtration units may not be helpful for reducing children’s health risks.House-specific and tailor-made control measures are critical in lowering indoor exposure to DEHP to promote sustainable buildings and children’s health in China.

Maslinic acid supplementation prevents di(2-ethylhexyl)phthalate-induced apoptosis via PRDX6 in peritubular myoid cells of Chinese forest musk deer

Chinese forest musk deer(FMD),an endangered species,have exhibited low reproductive rates even in captivity due to stress conditions.Investigation revealed the presence of di(2-ethylhexyl)phthalate(DEHP),an environmental endocrine disruptor,in the serum and skin of captive FMDs.Feeding FMDs with maslinic acid(MA)has been observed to alleviate the stress response and improve reproductive rates,although the precise molecular mechanisms remain unclear.Therefore,this study aims to investigate the molecular mechanisms underlying the alleviation of DEHP-induced oxidative stress and cell apoptosis in primary peritubular myoid cells(PMCs)through MA intake.Primary PMCs were isolated and exposed to DEHP in vitro.The results demonstrated that DEHP significantly suppressed antioxidant levels and promoted cell apoptosis in primary PMCs.Moreover,interfering with the expression of PRDX6 was found to induce excessive reactive oxygen species(ROS)production and cell apoptosis in primary PMCs.Supplementation with MA significantly upregulated the expression of PRDX6,thereby attenuating DEHP-induced oxidative stress and cell apoptosis in primary PMCs.These findings provide a theoretical foundation for mitigating stress levels and enhancing reproductive capacity of in captive FMDs.

孕早期增塑剂DEHP亚急性暴露影响蜕膜反应并增加流产风险

目的:探究邻苯二甲酸酯类增塑剂邻苯二甲酸二(2-乙基)己酯(DEHP)亚急性暴露对小鼠子宫内膜蜕膜反应和流产风险的影响。方法:分别选取300、1000、3000 mg·kg^(-1)·d^(-1)三个浓度梯度的DEHP对CD1小鼠进行经口亚急性暴露28 d。建立DEHP亚急性暴露小鼠早期自然妊娠模型和人工诱导假孕小鼠蜕膜反应模型,分别取自然妊娠第7天子宫组织和人工诱导蜕膜反应小鼠妊娠第8天诱导侧子宫组织,通过苏木精-伊红染色(HE染色)、Masson染色、TUNEL检测、蛋白质印迹法检测DEHP亚急性暴露对小鼠蜕膜反应的影响。构建300 mg·kg^(-1)·d^(-1) DEHP亚急性暴露小鼠自然流产模型,观察妊娠第10天的妊娠结局,探究蜕膜反应受损对小鼠妊娠的影响。结果:与空白对照组比较,DEHP大剂量组受孕率显著性降低(P<0.05);HE染色显示DEHP小剂量组和中剂量组蜕膜基质细胞排列杂乱、细胞核形态不规则、胞浆染色不均、多核细胞数显著降低;Masson染色显示DEHP小剂量组和中剂量组蜕膜组织的胶原纤维分布更多、数量增多、排列杂乱;TUNEL检测显示暴露组蜕膜组织细胞凋亡增加;蛋白质印迹法检测显示暴露组子宫内膜蜕膜反应标志分子BMP2蛋白表达水平显著降低(P<0.05或P<0.01);在米非司酮流产刺激下DEHP小剂量组小鼠流产率、胚胎吸收率显著升高,胚胎数、子宫湿重、子宫面积、胎盘湿重显著减少(P<0.05或P<0.01)。结论:DEHP亚急性暴露导致小鼠子宫内膜蜕膜反应受损加重小鼠妊娠流产风险。