Brief maternal exposure of rats to the xenobiotics dibutyl phthalate or diethylstilbestrol alters adult-type Leydig cell development in male offspring

Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate （DBP; from gestational day （GD） 14.5 to postnatal day （PND） 6） or diethylstilbestrol （DES; from GD14o5 to GD16.5） during a short gestationalllactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.

Combined Subchronic Toxicity of Bisphenol A and Dibutyl Phthalate on Male Rats

Objective To evaluate the combined subchronic toxicity of bisphenol A（BPA） and dibutyl phthalate（DBP） in male Sprague Dawley（SD） rats.Methods Forty 4‐week‐old male rats weighing 115‐125 g were randomly divided into BPA‐treated,DBP‐treated group,BPA＋DBP‐treated and control groups and fed with a soy‐ and alfalfa‐free diet containing 285.4 ppm BPA,285.4 ppm DBP,285.4 ppm BPA plus 285.4 ppm DBP,and a control diet,respectively,for 90 consecutive days.At the end of the study,the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed.Organs,including liver,kidneys,spleen,thymus,heart,brain,and testis underwent pathological examination.The androgen receptor（AR）,gonadotropin‐releasing hormone receptor（GNRHR）,and progesterone hormone receptor（PR） genes from the hypothalamus were detected by real‐time PCR.The biomedical parameters were analyzed.Results No significant difference was found in food intake,body weight,tissue weight,organ/brain weight ratio,and biomedical parameters among the four groups（P〉0.05）.However,BPA and DBP up‐regulated AR,PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA＋DBP group.Conclusion The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.

Uncertainty Evaluation for the Determination of Dibutyl Phthalate(DBP) Concentration in Liqueur by GC-MS

The dibutyl phthalate （DBP） concentration in liqueur was measured by gas chromatography-mass spectrometry （GC-MS）, and the uncertainty during the mea-surement was evaluated in this study. The results showed that the combined stan-dard uncertainty was determined as 0.028 and the expanded uncertainty was 0.056 at confidence probability p=95%, coverage factor k=2, by fol owing the methods de-scribed in GB/T 21911-2008 ＂Determination of Phthalate Esters in Foods＂. The av-erage DBP concentration in the liqueur of eight repeated measurements was（0.985＆#177; 0.056） mg/kg finaly.

Whole genome sequencing exploitation analysis of dibutyl phthalate by strain Stenotrophomonas acidaminiphila BDBP 071

Dibutyl phthalate(DBP)is widely used as a plasticizer in plastic food packaging and has attracted extensive attention due to its residual hazards and ability to accumulate.Microbial degradation is a very effective way to remove DBP from a polluted environment.In this study,Stenotrophomonas acidaminiphila BDBP 071,a strain that efficiently degraded DBP was isolated from tomato rhizosphere soil.To obtain a comprehensive understanding of the degradation mechanism of DBP by S.acidaminiphila strain BDBP 071,whole genome sequencing of this strain was performed.The results showed that the genome size of BDBP 071 was 3.87 Mb,the G+C content was 69.43%,and the number of predicted coding sequences was 3484.Based on whole genome sequencing,the metabolic pathway related to DBP biotransformation was obtained,and key genes were subsequently verified by a real-time quantitative polymerase chain reaction to infer the degradation pathway of DBP.It was preliminarily predicted that the relative expression of monoester hydrolase of EstB3 is increased in this strain.This study provides a scientific basis for applying S.acidaminiphila BDBP 071 in environmental pollution bioremediation,as well as a rich resource for DBP biodegradation genes.

Dibutyl phthalate disrupts[Ca^(2+)]_(i),reactive oxygen species,[pH]_(i),protein kinases and mitochondrial activity,impairing sperm function

To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse spermatozoa.At 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]i.Interestingly,DBP showed biphasic effects on[pH]i.DBP at 10–100μg/mL significantly decreased sperm motility.Similarly,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm motility.DBP significantly increased ROS and LPO.DBP at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by DBP.DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins.DBP at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm capacitation.Altogether,DBP showed a biphasic effect on intracellular signaling in spermatozoa.At concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm capacitation.DBP at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility.

Chemical Constituents of Angelica sinensis

Aim To investigate the active constituents responsible for thepharmacological activities of Angelica sinensis (Oliv) Diels. Methods Chromatography was used toisolate chemical components, and spectroscopy was used to identify their structures. Results Sevencompounds were isolated and their structures were identified as ferulic acid (1), conife-rylferukte(2) , bis (2-ethylhexyl) phthalate (3), dibutyl phthalate (4), lignoceric acid (5), palmitic acid(6), and Z-6, 7-cis-dihydroxyligustilide (7) Conclusion Bis (2-ethylhexyl) phthalate and dibutylphthalate were obtained from Angelica sinensis for the first time.

Food emulsifier glycerin monostearate aggravates phthalates'testicular toxicity by disrupting tight junctions'barrier function in rats

Objectives:This study aimed to investigate the effect of the widely used food emulsifier glycerin monostearate(GM)on testicular toxicity caused by the mixture of three commonly used phthalate esters(MPEs)in rats,and further to explore the underlying mechanism.Materials and Methods:Thirty male Sprague-Dawley rats were randomly divided into three groups.Rats were orally treated with 160 mg/kg/d MPEs in the MPEs group;coinstantaneously treated with 160 mg/kg/d MPEs and 200 mg/kg/d GM in the MPEs+GM group;and treated with the excipient in the control group.The intervention lasted for 5 weeks.Testis weight,epididymis weight,testicular histopathology,and serum testosterone were detected for testicular toxicity evaluation.The testicular ultrastructure,the tight junction proteins zonula occluden(ZO)-1,and claudin were measured for the mechanism exploration.Results:The body weight,epididymis,serum testosterone level,and anogenital distance in the MPEs+GM group were significantly decreased compared with control group(P<0.05);Testicular histopathological observation showed that shed spermatids were observed in the MPEs+GM group.Ultrastructural observation of testicular cells showed that the cristae number was decreased in some mitochondria in the MPEs group,whereas the cristae were fused and disappeared in most mitochondria in the MPEs+GM group.The tight junctions were broken in the MPEs+GM group;meanwhile,the expression of ZO-1 and claudin were altered in the MPEs+GM group(P<0.01).Conclusions:The results from this study indicated that GM aggravated MPEs'testicular toxicity,which might relate to the injured mitochondria and damaged tight junctions in testicular tissue.