Impact Of Neonatal Exposure To Different Doses Of Bisphenol A On The Hypothalamic-pituitary-testicle Axis In Male Rat

Objective:To observe the hypothalamic kiss-1 and the testis androgen acceptor(AR) gene expression changes and the level of serum luteinizing hormone(LH), follicle stimulating hormone(FSH), testosterone(T) and Inhibin B(INH B)exposure to different doses of bisphenol-A(BPA)in neonatal. In order to explore the effects of neonatal exposure to different doses of bisphenol A on the hypothalamic-pituitary-testis axis and the testis function in toddler and adolescent male rat.Methods:Eighty neonatal male Sprague-Dawley(SD) rats were randomly divided into five groups: blank control, vehicle, low-dose BPA(25ug/(kg.d)), medium-dose BPA(50ug/(kg.d)) and high-dose BPA(250 ug/(kg.d)). The rats were subcutaneously injected with respective agents in the back of neck on postnatal days 1-7(PND1-7). Pups were weaning on postnatal days 21(PND21) and respectively and randomly sacrificed the half on postnatal days 22(PND 22, the toddler) and PND 50(the adolescent), and the blood were collected by the heart punctures. The hypothalamus and testis were taken and weighed. The hypothalamic Kiss-1 m RNA and the testis androgen acceptor m RNA were measured by Real-Time PCR. The level of serum luteinizing hormone, follicle stimulating hormone and testosterone were measured by radioimmunoassay and Inhibin B(INH B) by enzyme-linked immunosorbent assay.Results:1. The impact on rats weight:there was no significant difference between the control group and other five drug groups on the weight of rats in PND 1,7,22,50(P>0.05). 2. The results of the organ coefficient, the organ coefficient of hypothalamus was not different between the experimental groups and the blank control group in PND22 and PND50(P>0.05). The medium-dose and high-dose BPA groups compared with the controls, the organ coefficient of testis decreased significantly in PND 50(P<0.05),while there was no significant difference in the organ coefficient of testis compared the treatment groups to the controls(P>0.05). 3. On the results of the serum pituitary hormone levels, In PND22 and PND50 male offspring, the serum LH and FSH of treatment groups decreased compared with control group, in PND22 male pups, the medium-dose and high-dose BPA groups compared with the controls, the level of serum LH and FSH were decreased significantly(P <0.05), while there was no significant difference in PND50(P> 0.05). 4. From the results of serum sex hormone levels,the medium- dose and high-dose BPA groups compared with the controls, the level of serum T obviously decreased in PND22 and PND50(P<0.05). In PND22 and PND50 male offspring, the serum INH B of treatment groups also decreased compared with control group, but there was no significant(P> 0.05). 5.From the results of Real-Time-PCR, in high-dose group of PND 22, the expression of hypothalamic Kiss-1 m RNA increased compared with the rest of the groups(P<0.05),while in PND50, compared with control group,the medium- and high-dose groups Kiss-1m RNA decreased(P<0.05). In the groups of vehicle,25ug/(kg.d), 50ug/(kg.d)and250ug/(kg.d) BPA, there were no significant difference in the m RNA expressions of testis androgen acceptor(AR) with control group in PND 20 and PND 50(P>0.05).Conclusions:1. Daily subcutaneous different doses of bisphenol A injection had no great effection on body weights of the male rats on postnatal days 1,7,20 and 50. 2. Neonatal exposure to the low-dose BPA does not have a significantly influence on the hypothalamus–pituitary- testis axis and the testis function. 3. Neonatal exposure to the medium- and high-dose BPA affect the expression level of the hypothalamic kiss-1m RNAin toddler and adolescent male rat. 4. Neonatal exposure to the medium- and high-dose BPA may impair the function of testisin toddler and adolescent male rat, and affect the function of the hypothalamus–pituitary-testis axis.