Effect of exposure to different doses of Bisphenol A during neonate on hypothalamic-pituitary- testis axis in male rats

Abstract

Objective To explore the effect of neonatal exposure to different doses of Bisphenol A (BPA) on the hypothalamic-pituitary-testis axis in toddler and adolescent male rats. Methods Neonatal male Sprague-Dawley rats were randomly divided into 5 groups through random digital table method: control group, vehicle group, low-dose BPA [25 μg/(kg·d)] group, medium-dose BPA[50 μg/(kg·d)] group and high-dose BPA [250 μg/(kg·d)] group.The rats were subcutaneously injected with respective agents on postnatal days 1-7 (PND 1-7). Pups were sacrificed on PND 22 and PND 50.The hypothalamus and testis were taken and weighed.The hypothalamic Kiss-1 mRNA and the testis androgen receptor (AR) mRNA were tested by using real-time fluorescence quantitative and the levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) were tested by using radio immunity method, and inhibin B was measured by using enzyme linked immunosorbent assay. Results Compared with the controls, the level of serum FSH [(1.610 0±0.693 2) IU/L, (1.574 3±0.675 0) IU/L vs (2.362 9±0.580 3) IU/L](F=3.314, P=0.026), LH [(3.876 3±0.908 0) IU/L, (3.603 8±1.350 2) IU/L vs (5.302 5±0.768 4) IU/L](F=3.139, P=0.027) and T [(0.383 8±0.177 8) μg/L, (0.442 5±0.214 1) μg/L vs (0.782 5±0.282 1) μg/L](F=5.106, P<0.01) of medium and high-dose BPA groups, were decreased in PND 22, and the organ coefficient of testis [(0.952 90±0.049 15)%, (0.969 20±0.045 82)% vs (1.022 80±0.011 08)%](F=10.326, P<0.01)and serum T [(1.758 6±0.369 6) μg/L, (1.718 8±0.395 7) μg/L vs (3.357 5±0.749 8) μg/L](F=13.799, P=0.012) were significantly decreased in PND 50.In high-dose BPA group of PND 22, the expression of hypothalamic Kiss-1 mRNA (0.068 80±0.011 79) was increased compared with the other groups(F=272.125, P<0.01), while in PND 50, compared with control group, the Kiss-1 mRNA(0.002 00±0.000 25, 0.001 90±0.000 48 vs 0.001 40±0.000 17) of medium- and high-dose BPA groups was decreased(F=191.826, P<0.01). Conclusions Neonatal exposure to the medium and high-dose BPA may impair the function of testis in toddler and adolescent male rats, and affect the hypothalamus-pituitary-testis axis.Neonatal exposure to the low-dose BPA does not have a significant influence on the hypothalamus-pituitary- testis axis. Key words: Bisphenol A; Hypothalamic-pituitary-testicle axis; Neonatal male rat