Ding Yongbo, Yu Jianhong, Qu Pingping, Ma Piliang, Yu Zhenyu
a Department of Anesthesiology , Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College , Yantai , China .
b Department of Anesthesiology , Yantai Affiliated Hospital of Binzhou Medical University , Yantai , China , and .
Inhal Toxicol. 2015;27(12):621-8. doi: 10.3109/08958378.2015.1080772. Epub 2015 Sep 10.
This study aims to investigate the negative effects of chronic exposure to isoflurane on spermatogenesis and explore the underlying mechanisms. Sixty male rats were randomly allocated to two groups: control group, receiving no treatment, and anesthesia group, administrated exposure to isoflurane (2 ppm) for 25 consecutive days (1 h/day). The negative effects of chronic exposure to isoflurane were evaluated by analyzing the median eminence GnRH content, the relevant hormone levels, some sperm parameters and the mRNA expressions for some reproduction-related genes. Isoflurane significantly decreased the GnRH content and the serum gonadotrophin levels compared with the control group (p<0.01). Meanwhile, the mRNA expressions of GnRH in hypothalamus, GnRH receptor, luteinizing hormone (LH)-β and follicle-stimulating hormone (FSH)-β in pituitary, and LH receptor and FSH receptor in testes were also significantly inhibited (p<0.01). Furthermore, the mRNA expressions of androgen receptor (AR), kisspeptin encoded gene (Kiss-1) and its receptor (GPR54) in hypothalamus were significantly diminished by isoflurane (p<0.01). The results indicated that chronic exposure to isoflurane diminished the synthesis and secretion of GnRH by inhibiting the androgen-AR-Kisspeptin-GPR54 pathway and breaking the hypothalamic-pituitary-gonadal equilibrium, and therefore it could inhibit spermatogenesis.
本研究旨在探讨慢性暴露于异氟烷对精子发生的负面影响，并探索其潜在机制。将60只雄性大鼠随机分为两组：对照组，不接受任何处理；麻醉组，连续25天（每天1小时）暴露于异氟烷（2 ppm）。通过分析正中隆起促性腺激素释放激素（GnRH）含量、相关激素水平、一些精子参数以及一些生殖相关基因的mRNA表达，评估慢性暴露于异氟烷的负面影响。与对照组相比，异氟烷显著降低了GnRH含量和血清促性腺激素水平（p<0.01）。同时，下丘脑GnRH、垂体GnRH受体、黄体生成素（LH）-β和卵泡刺激素（FSH）-β以及睾丸中LH受体和FSH受体的mRNA表达也受到显著抑制（p<0.01）。此外，异氟烷显著降低了下丘脑雄激素受体（AR）、亲吻素编码基因（Kiss-1）及其受体（GPR54）的mRNA表达（p<0.01）。结果表明，慢性暴露于异氟烷通过抑制雄激素-AR-亲吻素-GPR54途径并打破下丘脑-垂体-性腺轴平衡，减少了GnRH的合成和分泌，从而抑制精子发生。
