Semen Cuscutae Flavonoids And Other Herbals Ameliorate The Reproductive Toxicity In Offspring Mice Induced By Bisphenol A

Bisphenol A?BPA?is one of the ubiquitous environmental endocrine disrupters?EEDs?,which has an adverse effect on reproductive hormones,cell apoptosis and so on.However,the mechanism of BPA toxicity is not clearly understood so far.In order to investigate how gestational exposure to bisphenol A induces reproductive toxicity in offspring mice and semen cuscutae flavonoids and other herbals ameliorate the toxicity,pregnant kunming mice were given different dosages of BPA from pregnancy day?PND?8to PND 14.The offspring mice?male and female?were sacrificed at 8 weeks of age.Then,the histopathological changes of testis and ovaries,the levels of reproductive hormones?follicle stimulating hormone,FSH;luteinizing hormone,LH;Estrogen,E₂;Testosterone,T?,the Bax and Bcl-2 apoptosis proteins levels in testis and ovaries,Cholesterol Side ChainCleavageEnzymeGene?CYP11??,SteroidAcuteRegulator?StAR?,kit-lignad?Kitlg?,and Anti-mullerian hormone?AMH?,in offspring mice were detected.The pregnant mice body weight,ovary morphology and offspring death rate were calculated when weaning.We also studied the protective effect of Seman Cuscutae Flavonoids?SCF?,Lycopene?Lyc?and Baicalin?Bai?on the reproductive toxicity induced by BPA.To confirm the protective effect of SCF,Lyc and Bai on the male toxicity induced by BPA in vitro,the TM3 cells were treated with BPA after SCF,Lyc and Bai respectively,and the level of T and StAR was detected.1.The reproductive toxicity of BPA in offspring and maternal mice:according to the foreign references?BPA at 600 mg/kg BW?and our own pretrial results,we selected the oral dose of BPA in this study as 500 mg/kg BW.The reproductive toxicity on offspring male mice showed that,the hormone level of T was decreased,the testis morphology was disordered seriously.High level of Bax and low level of Bcl-2 in testis,decreased mRNA expression of StAR,and increased CYP11?mRNA were observed when compared to the control group.The reproductive toxicity in offspring female mice showed that,the level of FSH and LH was decreased,the E₂ was increased,the morphology of ovaries was disordered severely.The high level of Bax and the low level of Bcl-2 in ovaries,the increased mRNA expression of AMH,and the decreased mRNA expression of Kitlg were observed when compared to the control group.Treated with 500 mg/kg BPA,the body weight of pregnant mice was decreased,the morphology of ovaries was disordered and the death rate of offspring mice was increased compared to the control group?P<0.01?.2.Protective effects of Semen Cuscutae Flavonoids and other herbals on reproductive damage in offspring mice induced by Bisphenol A:the reproductive toxicity of BPA in offspring mice was ameliorated when pretreated with Chinese herbal components Semen Cuscutae Flavonoids?SCF?,Lycopene?Lyc?and Baicain?Bai?from Gestation Day?GD?1to GD 7.Results of male offspring mice showed that,SCF,Lyc and Bai could increase the hormone level of T,and protect the integrity of testis when compared to the BPA group.In SCF group the protein and mRNA expression of StAR,CYP11?,Bcl-2 were increased and Bax mRNA was decreased compared to the BPA group.Protein expression of Bax was decreased,Bcl-2 was increased,and mRNA expression of StAR,CYP11?and Bcl-2 was increased in Lyc group when compared to the BPA group.Protein expression of CYP11?and Bcl-2 were increased,Bax was decreased,and mRNA expression of Bcl-2 was increased in Bai group when compared to the BPA group.Results of female offspring mice showed that SCF,Lyc and Bai could protect the integrity of ovaries.SCF could increase the hormone levels of FSH and LH,decrease the level of E₂,and also decrease the protein expression of AMH,Bax and apoptosis,increase the mRNA expression of Kitlg and Bcl-2,decrease the mRNA expression of AMH and Bax when compared to the BPA group.The Chinese herbal of Lyc could increase the hormone level of LH,decrease the hormone level of E₂,and also decrease the protein expression of AMH,Bax and apoptosis,increase the protein expression of Bcl-2,increase the mRNA expression of Kitlg,decrease the mRNA expression of AMH when compared to the BPA group.Bai could increase the hormone level of FSH and LH,decrease the hormone level of E₂,and also decrease the protein expression of AMH,increase the protein expression of Bcl-2,and the mRNA expression of AMH decreased when compared to the BPA group.Lyc could increase the body weight of pregnant mice,decrease the offspring mice death rate,and protect the organization structure of the ovary.3.Protective effects of Semen Cuscutae Flavonoids and other herbals on reproductive damage in TM3 cell induced by Bisphenol A:the in vitro results showed that pretreatment of TM3 cells with SCF,Lyc and Bai could increase the level of T and protein expression of StAR,and protect the TM3 cell from the toxicity of BPA.In summary,our results showed that maternal exposure to BPA could disturb reproductive hormones,induce leydig cells and granular cells apoptosis in offspring mice.The major mechanism is that BPA disrupts protein and mRNA expression related to hormones synthesis,resulting in leydig cells and granular cells apoptosis,and abnormal level of reproductive hormones.Different Chinese herbals such as SCF,Lyc and Bai could reverse the toxicity of BPA,normalize protein and mRNA expression related to synthesis hormones,and protect leydig cells and granular cells from apoptosis.SCF,Lyc and Bai could ameliorate the reproductive toxicity of offspring mice induced by BPA.