2,3',4,4',5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells.

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 µg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.

Adsorption of sulfur on Au(111) surface: An extremely stable configuration.

The sulfur adsorption on gold surface is a hot topic in catalysis, electrochemistry and chemical sensors. However, the multiple structures of adsorbed sulfur and sulfur-induced reconstruction in gold substrate topography are still open problems until now. Here we performed an extensively study on sulfur adsorption on Au(111) surface based on First-Principles calculation. Our results show that the sulfur adsorption with additional Au atoms is not favorable. Thus, the well-known lifting of the herringbone reconstruction of Au(111) after sulfur adsorption can't be attributed to the lifting gold atoms. More importantly, we proposed an extremely stable configuration of S-Au(111) surface characterized by (√3 × âˆš3)R30° at 0.33 coverage, in which each S atom is chemisorbed in 3-fold coordinated sites and all the surface-Au atoms are terminated. Finally, the good agreement between our simulated STM and LEED images and experimental observations illuminates the truth that our proposed configuration is also favorable in experiment. This super stable S-adsorbed surface can be used as a starting point for the growth of two dimensional transition metal sulfides.

Effect of Ligand Structures on Ligand-Protected Gold Clusters: [Au-(p-/m-/o-MBT)]1-8 Clusters.

The controllable preparation of ligand-protected clusters is still an unresolved problem, which may be due to that their formation mechanism is unclear. We propose that the ligand is the key to solve the above problems. Here, by using p-, m-, and o-methylbenzenethiol ligand protected gold clusters as examples, we try to explore the effect of ligand structures on ligand-protected gold clusters. The geometrical structures, relative stabilities and surface properties of small-sized ligand-protected gold clusters [Au-SR]1-8 (SR = p-/m-/o-MBT) have been systematically studied based on the density functional theory. The results show that the ground state structures of [Au-SR]1-8 clusters tend to form closed rings except for [Au-SR]1,2. The different structures of ligand have significant effect on the structures and stabilities of ligand-protected clusters. By analyzing their surface properties and possible growth patterns, it is found that [Au-SR]1,2 clusters serve as the basic building blocks, and the larger clusters can be regarded as the combinations of them. This study provides some insights into the effect of ligands on ligand-protected clusters, which is useful for understanding the formation mechanism of ligand-protected clusters.

Single-cell RNA sequencing reveals abnormal fluctuations in human eight-cell embryos associated with blastocyst formation failure.

Infertility has become a global health issue, with the number of people suffering from the disease increasing year by year, and ART offering great promise for infertility treatment. However, the regulation of early embryonic development is complicated and a series of processes takes place, including the maternal-to-zygotic transition. In addition, developmental arrest is frequently observed during human early embryonic development. In this study, we performed single-cell RNA sequencing on a biopsied blastomere from human eight-cell embryos and tracked the developmental potential of the remaining cells. To compare the sequencing results between different eight-cell embryos, we have combined the research data of this project with the data previously shared in the database and found that cells from the same embryo showed a higher correlation. Additionally, the transcriptome of embryos with blastocyst formation failure was significantly different from developed embryos, and the gene expression as well as cell signaling pathways related to embryonic development were also altered. In particular, the expression of some maternal and zygotic genes in the failed blastocyst formation group was significantly altered: the overall expression level of maternal genes was significantly higher in the failed blastocyst than the developed blastocyst group. In general, these findings provide clues for the causes of human embryonic arrest after the eight-cell stage, and they also provide new ideas for improving the success rate of ART in clinical practice.

Intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl alters spermatogenesis and testicular DNA methylation levels in F1 male mice.

Polychlorinated biphenyls (PCBs) are synthetic biphenyl compounds with high toxicity. There are a total of 209 homologs, among which 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the dioxin-like PCBs. PCB118 can accumulate in pregnant mice, leading to fetus directly exposure during development. The stage of migration of mouse primordial germ cells ranges from 8.5 to 13.5 days of pregnancy, which is the stage undergoing a genome-wide DNA demethylation process. In this study, the mice were exposed to 20 µg/kg/day and 100 µg/kg/day PCB118 from 8.5 to 13.5 days of pregnancy. During the embryo stage at 18.5 days (E18.5 days), the expression level of DNA methyltransferase 1 (Dnmt1) was reduced in the testes, and the DNA methylation level in mouse testes were also decreased. We found that the seminiferous tubules showed vacuolization and that the sperm deformity rate increased in the treated groups compared with the control group in 7-week-old mice. Because exposure to PCB118 during pregnancy causes damage to the reproductive system of male offspring mice, attention should be devoted to the toxicity transmission of persistent environmental pollutants such as PCBs.

Effects of Polychlorinated Biphenyls on Animal Reproductive Systems and Epigenetic Modifications.

Polychlorinated biphenyls (PCBs) are a group of highly toxic endocrine-disrupting chemicals comprising 209 homologs. PCBs are extensively found in the environment and can induce typical estrogenic and profound, long-lasting effects on animals. In this article, the introduction of PCB residues into the environment and the pathways of PCB enrichment in animals are described. PCBs are widely deposited and eventually accumulate in human tissues and body fluids through biomagnification. PCBs can significantly decrease animal fertility and interfere with endocrine processes, leading to the development of various diseases and even cancer. The effects of PCBs on the reproductive systems of animals can also be passed to their offspring, indicating that PCBs may affect the epigenetic modification process. There is currently no treatment to effectively inhibit the toxicity of PCBs in organisms; therefore, the severity of PCB toxicity needs to be widely recognized.

Effects of 2,3',4,4',5-pentachlorobiphenyl exposure during pregnancy on DNA methylation in the testis of offspring in the mouse.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants, and the widespread use of PCBs has had adverse effects on human and animal health. This study experiment explored the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on the mammalian reproductive system. PCB118 was administered to pregnant mice from 7.5 to 12.5 days of gestation; F1 mice were obtained and the reproductive system of F1 male mice was examined. PCB118 damaged the reproductive system in male F1 mice, as evidenced by negative effects on the testicular organ coefficient (testes weight/bodyweight), a decrease in the diameter of seminiferous tubules and a significant reduction in the anogenital distance in 35-day-old F1 mice. In addition, methylation levels of genomic DNA were reduced, with reductions in the expression of the DNA methyltransferases DNMT1, DNMT3A and DNMT3B, as well as that of the epigenetic regulatory factor ubiquitin like with PHD and ring finger domains 1 (Uhrf1). Together, the results of this study provide compelling evidence that exposure of pregnant mice to PCB118 during primordial germ cell migration in the fetus affects the reproductive system of the offspring and decreases global methylation levels in the testis.

Effects of intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring.

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 µg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development.

BRG1-associated factor 250a (BAF250a) is a component of the SWI/SNF adenosine triphosphate-dependent chromatin remodeling complex, which has been shown to control chromatin structure and transcription. BAF250a was reported to be a key component of the gene regulatory machinery in embryonic stem cells controlling self-renewal, differentiation, and cell lineage decisions. Here we constructed Baf250aF/F ;Gdf9-cre (Baf250aCKO ) mice to specifically delete BAF250a in oocytes to investigate the role of maternal BAF250a in female germ cells and embryo development. Our results showed that BAF250a deletion did not affect folliculogenesis, ovulation, and fertilization, but it caused late embryonic death. RNA sequencing analysis showed that the expression of genes involved in cell proliferation and differentiation, tissue morphogenesis, histone modification, and nucleosome remodeling were perturbed in Baf250aCKO MII oocytes. We showed that covalent histone modifications such as H3K27me3 and H3K27ac were also significantly affected in oocytes, which may reduce oocyte quality and lead to birth defects. In addition, the DNA methylation level of Igf2r, Snrpn, and Peg3 differentially methylated regions was decreased in Baf250aCKO oocytes. Quantitative real-time polymerase chain reaction analysis showed that the relative messenger RNA (mRNA) expression levels of Igf2r and Snrpn were significantly increased. The mRNA expression level of Dnmt1, Dnmt3a, Dnmt3l, and Uhrf1 was decreased, and the protein expression in these genes was also reduced, which might be the cause for impaired imprinting establishment. In conclusion, our results demonstrate that BAF250a plays an important role in oocyte transcription regulation, epigenetic modifications, and embryo development.

Effects of 2,3',4,4'5-pentachlorobiphenyl exposure during pregnancy on epigenetic imprinting and maturation of offspring's oocytes in mice.

Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been widely found in the environment. The chemical 2,3',4,4'5-pentachlorobiphenyl (PCB118) is an important dioxin-like PCB compound with strong toxicity. PCB118 can accumulate in adipose tissue, serum and milk in mammals, and it is highly enriched in the follicular fluid. In this study, pregnant mice were exposed to 0, 20 and 100 µg/kg/day of PCB118 during pregnancy at the fetal primordial germ cell migration stage. The methylation patterns of the imprinted genes H19, Snrpn, Peg3 and Igf2r as well as the expression levels of Dnmt1, 3a, 3b and 3l, Uhrf1, Tet2 and Tet3 in fully grown germinal vesicle oocytes were measured in offspring. The rates of in vitro maturation, in vitro fertilization, oocyte spindle and chromosomal abnormalities were also calculated. The results showed that prenatal exposure to PCB118 altered the DNA methylation status of differentially methylated regions in some imprinted genes, and the expression levels of Dnmt1, 3a, and 3l, Uhrf1 and Tet3 were also changed. In addition, PCB118 disturbed the maturation process of progeny mouse oocytes in a dose-dependent manner. Therefore, attention should be paid to the potential impacts of PCB118-contaminated dietary intake during pregnancy on the offspring's reproductive health.

[Effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice].

OBJECTIVE: To study the effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice. METHOD: Eight male C57BL/6J mice were selected in the normal group (NF), 40 male ApoE -/- mice were fed for 16 weeks, divided into the model group (HF), the rosiglitazone group ( LGLT), the Jinlida low-dose group (JLDL), the Jinlida medium-dose group (JLDM), the Jinlida high-dose group (JLDH) and then orally given drugs for 8 weeks. The organization free fatty acids, BCA protein concentration determination methods were used to determine the skeletal muscle FFA content. The Real-time fluorescent quantitative reverse transcription PCR ( RT-PCR) and Western blot method were adopted to determine mRNA and protein expressions of mice fatty acids transposition enzyme (FAT/CD36), carnitine palm acyltransferase 1 (CPT1), peroxide proliferators-activated receptor α( PPAR α). RESULT: Jinlida could decrease fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG), free fatty acid (FFA) and fasting insulin (FIns) and raise insulin sensitive index (ISI) in mice to varying degrees. It could also up-regulate mRNA and protein expressions of CPT1 and PPARα, and down-regulate mRNA and protein levels of FAT/CD36. CONCLUSION: Jinlida can improve fat-induced insulin resistance ApoE -/- in mice by adjusting the changes in expression of skeletal muscle lipid transport enzymes.

Synthesis, biological evaluation, and molecular docking studies of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives as novel anticancer agents.

A series of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives (5a-8d) have been designed and synthesized, and their biological activities were also evaluated as potential antitumor and cyclin dependent kinase 2 (CDK2) inhibitors. Among all the compounds, compound 5a displayed the most potent CDK2/cyclin E inhibitory activity in vitro, with an IC(50) of 0.98 ± 0.06 µM. Antitumor assays indicated that compound 5a owned high antiproliferative activity against MCF-7 and B16-F10 cancer cell lines with IC(50) values of 1.88 ± 0.11 and 2.12 ± 0.15 µM, respectively. Docking simulation was performed to insert compound 5a into the crystal structure of CDK2 at active site to determine the probable binding model. Based on the preliminary results, compound 5a with potent inhibitory activity in tumor growth may be a potential anticancer agent.