Plasticizer DEHP induces female reproductive toxicity through changes in intestinal flora
Objective To observe the effect of plasticizer di-(2-ethylhexyl)phthalate(DEHP)on intestinal flora composition and ovarian function in SD rats,and to preliminarily explore the possible relationship between changes in intestinal flora and female reproductive toxicity.Methods Totally 30 SD rats were randomly divided into 5 groups,with 6 rats in each group,namely the corn oil control group and 5,50,500 and 2 500 mg/(kg·d)DEHP dosage groups.The rats were gavaged continuously for 14 days.The changes of serum anti-müllerian hormone(AMH)level and ovarian mass index in each group were compared after the experiment.Meanwhile,16S rRNA amplicon sequencing analysis was performed on rat feces.Results After DEHP exposure,the AMH levels in the control group and the 5,50,500,and 2 500 mg/(kg·d)dose groups were(5.41±0.39),(4.98±0.44),(4.99±0.12),(4.30±0.51)and(3.91±0.23)ng/mL,respectively,and the ovarian mass index was(0.058±0.002),(0.056±0.001),(0.052±0.002),(0.049±0.002)and(0.045±0.003)g/g.Compared with the control group,AMH levels and ovarian mass index were significantly reduced in all dose groups except the 5 mg/(kg·d)group(all P<0.05).Serum AMH levels were negatively correlated with the dose of DEHP exposure dose(P<0.01).Ovarian mass index of rats decreased in a dose-dependent manner after DEHP exposure.After DEHP exposure,the relative abundance of Firmicutes in the intestinal flora of rats decreased,while the relative abundance of Bacteroides increased,and the ratio of Firmicutes/Bacteroides decreased significantly(P<0.05).Firmicutes was the characteristic flora of DEHP dosage group,among which Enterobacteriaceae,Enterobacteriales,Lactobacillus,Ruminococcaceae and Lachnospiraceaeall had significant effects on the differences between groups(all P<0.05).Conclusion After exposure to DEHP,the structure of intestinal flora in rats changed and the ovarian function decreased.DEHP may induce female reproductive toxicity by changing the structure of intestinal flora.
Di-(2-ethylhexyl)phthalateIntestinal microorganismOvarian function