Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether...Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.展开更多
Developing alternatives to antibiotics for prevention of gastrointestinal dysbiosis in early-weaning farmed animals is urgently needed.This study was to explore the potential effects of trans-10,cis-12 conjugated lino...Developing alternatives to antibiotics for prevention of gastrointestinal dysbiosis in early-weaning farmed animals is urgently needed.This study was to explore the potential effects of trans-10,cis-12 conjugated linoleic acid(CLA)on maintaining ruminal homeostasis of young ruminants during the weaning transition period.Thirty neonatal lambs were selected(6 lambs per group)and euthanized for rumen microbial and epithelial analysis.The lambs were weaned at 28 d and experienced the following 5 treatments:euthanized on d 28 as the pre-weaning control(CON0),fed starter feed for 5(CON5)or 21(CON21)d,fed starter feed with 1%of CLA supplemented for 5(CLA5)or 21(CLA21)d.Results showed that the average daily weight gain and dry matter intake were significantly higher in CLA5 than CON5 group.As compared with the CON5 and CON21 group,the relative abundances of volatile fatty acid(VFA)producing bacteria including Bacteroides,Treponema,Parabacteroides and Anaerovibrio,as well as the concentrations of acetate,butyrate and total VFA were significantly increased in CLA5 and CLA21 group,respectively.Integrating microbial profiling and epithelial transcriptome results showed that 7 downregulated inflammatory signaling-related host genes IL2RA,CXCL9,CD4,CCR4,LTB,SPP1,and BCL2A1 with CLA supplementation were significantly negatively correlated with both VFA concentration and VFA producing bacteria,while 3(GPX2,SLC27A2 and ALDH3A1)and 2(GSTM3 and GSTA1)upregulated metabolism-related genes,significantly positively correlated with either VFA concentration or VFA producing bacteria,respectively.To confirm the effects of CLA on epithelial signal transduction,in vitro experiment was further conducted by treating rumen epithelial cells without or with IL-17A+TNF-αfor 12 h after pretreatment of 100μM CLA or not(6 replicates per treatment).The results demonstrated the anti-inflammatory effect of CLA via suppressing the protein expression of NF-кB p-p65/p65 with the activation of peroxisome proliferator-activated receptor gamma(PPARγ).In conclusion,CLA supplementation enhanced the ruminal microbiota-driven transcriptional regulation in healthy rumen epithelial development via rumen VFA production,and CLA may therefore serve as an alternative way to alleviate early-weaning stress and improve physiological and metabolic conditions of young ruminants.展开更多
基金supported by the National Key R&D Program of China(grant number 2021YFC2701100 and 2021YFC2701102)China-U.S.Program for Biomedical Collaborative Research(NSFCNIH)(grant number 81961128022)+1 种基金the National Natural Science Foundation of China(grant number 81903351)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.
基金This work was supported by the National Natural Science Foundation of China(No.31702133)the Central Public-interest Scientific Institution Basal Research Fund of Chinese Academy of Agricultural Sciences(No.Y2021GH18-2).
文摘Developing alternatives to antibiotics for prevention of gastrointestinal dysbiosis in early-weaning farmed animals is urgently needed.This study was to explore the potential effects of trans-10,cis-12 conjugated linoleic acid(CLA)on maintaining ruminal homeostasis of young ruminants during the weaning transition period.Thirty neonatal lambs were selected(6 lambs per group)and euthanized for rumen microbial and epithelial analysis.The lambs were weaned at 28 d and experienced the following 5 treatments:euthanized on d 28 as the pre-weaning control(CON0),fed starter feed for 5(CON5)or 21(CON21)d,fed starter feed with 1%of CLA supplemented for 5(CLA5)or 21(CLA21)d.Results showed that the average daily weight gain and dry matter intake were significantly higher in CLA5 than CON5 group.As compared with the CON5 and CON21 group,the relative abundances of volatile fatty acid(VFA)producing bacteria including Bacteroides,Treponema,Parabacteroides and Anaerovibrio,as well as the concentrations of acetate,butyrate and total VFA were significantly increased in CLA5 and CLA21 group,respectively.Integrating microbial profiling and epithelial transcriptome results showed that 7 downregulated inflammatory signaling-related host genes IL2RA,CXCL9,CD4,CCR4,LTB,SPP1,and BCL2A1 with CLA supplementation were significantly negatively correlated with both VFA concentration and VFA producing bacteria,while 3(GPX2,SLC27A2 and ALDH3A1)and 2(GSTM3 and GSTA1)upregulated metabolism-related genes,significantly positively correlated with either VFA concentration or VFA producing bacteria,respectively.To confirm the effects of CLA on epithelial signal transduction,in vitro experiment was further conducted by treating rumen epithelial cells without or with IL-17A+TNF-αfor 12 h after pretreatment of 100μM CLA or not(6 replicates per treatment).The results demonstrated the anti-inflammatory effect of CLA via suppressing the protein expression of NF-кB p-p65/p65 with the activation of peroxisome proliferator-activated receptor gamma(PPARγ).In conclusion,CLA supplementation enhanced the ruminal microbiota-driven transcriptional regulation in healthy rumen epithelial development via rumen VFA production,and CLA may therefore serve as an alternative way to alleviate early-weaning stress and improve physiological and metabolic conditions of young ruminants.
