School of Public Health, Fudan University, P.O. Box 288, 130 DongAn Road, Shanghai 200032, China.
Environ Toxicol. 2011 Nov;26(6):657-68. doi: 10.1002/tox.20677. Epub 2011 Mar 3.
In this study, we investigated the time-course changes of hormone levels and sperm numbers in male Sprague-Dawley (SD) rats after neonatal exposure to 3,3',4,4',5,5'-hexachlorobiphenyl (PCB169). Neonatal rats were given (through oral gavages) doses of 0, 0.025, 0.25, or 0.5 mg/kg-day of PCB169 in corn oil from postnatal day 1 (PND1) to PND7. The rats were sacrificed at PND8, PND21, and PND90. PCB169 exposure was confirmed by the marked induction of liver CYP1A1 mRNA expression at these three time points. The testicular daily sperm production and the sperm counts of the epididymis cauda significantly decreased at PND90 compared to that of control. Although reductions in serum thyroxine and triiodothyronine levels occurred at all these three time points and at both PND21 and PND90, respectively, the mRNA expression of testicular thyroid hormone receptor α1 was suppressed significantly only at PND8. The serum and testicular testosterone (T) levels declined markedly at PND90 compared to the controls, but there was no effect at PND21. The mRNA expression of testicular steroidogenic factor 1 was inhibited markedly at the three time points, whereas those of StAR, P450c17, P450scc, and 3β-HSD were suppressed significantly only at PND90 relative to the controls. PCB169 treatment had no effects on pituitary follicle-stimulating hormone and luteinizing hormone levels and on their receptors' expression in the testes. These results indicate that neonatal exposure to PCB169 damages hormone levels and testicular function in the long-term, resulting in persistent hypothyroidism and decreases in adult T levels and sperm counts.
在这项研究中，我们调查了雄性 Sprague-Dawley（SD）大鼠在新生儿期暴露于 3,3',4,4',5,5'-六氯联苯（PCB169）后激素水平和精子数量的时间变化。新生大鼠从出生后第 1 天（PND1）至 PND7 每天通过口服灌胃接受 0、0.025、0.25 或 0.5mg/kg-day 的 PCB169 溶于玉米油。在 PND8、PND21 和 PND90 处死大鼠。在这三个时间点，PCB169 暴露通过明显诱导肝 CYP1A1 mRNA 表达得到证实。与对照组相比，PND90 时睾丸每日精子生成和附睾尾部精子计数明显减少。虽然血清甲状腺素和三碘甲状腺原氨酸水平在这三个时间点以及 PND21 和 PND90 时均降低，但只有在 PND8 时，睾丸甲状腺激素受体α1 的 mRNA 表达受到显著抑制。与对照组相比，PND90 时血清和睾丸睾酮（T）水平明显下降，但 PND21 时没有影响。在三个时间点，睾丸甾体生成因子 1 的 mRNA 表达受到明显抑制，而 StAR、P450c17、P450scc 和 3β-HSD 的 mRNA 表达仅在 PND90 时相对于对照组受到显著抑制。PCB169 处理对垂体促卵泡激素和黄体生成素水平及其在睾丸中的受体表达没有影响。这些结果表明，新生儿期暴露于 PCB169 会长期损害激素水平和睾丸功能，导致持续性甲状腺功能减退以及成年 T 水平和精子计数降低。
