Department of Pain, Linzi District People's Hospital, Zibo, China.
Department of Obstetrics, Yantaishan Hospital, Yantai, China.
Inhal Toxicol. 2019 Sep-Oct;31(11-12):392-398. doi: 10.1080/08958378.2019.1698677. Epub 2019 Dec 5.
To study the effects of sevoflurane on reproductive function and its main mechanism of action in male rats. Forty adult male Sprague-Dawley rats were divided into 4 groups and exposed to 0, 50, 300 and 1800 ppm of sevoflurane, respectively. After 15 days, the serum levels of sex hormones and inflammatory factors were detected using enzyme-linked immunosorbent assay. Left testis was taken for conventional histopathological examination and TUNEL staining. Right testis was used for sperm production and daily sperm count were evaluated daily. Johnsen score was used to categorize the spermatogenesis. The expression of related genes in the hypothalamic-pituitary-gonadal axis were analyzed by quantitative real time polymerase chain reaction (qRT-PCR). Exposure to sevoflurane increased the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein 1 (MCP-1), decreased the content of serum testosterone (T), reduced the concentration of testicular sperm, the production of daily sperm and Johnsen score, and damaged vas deferens in a dose dependent manner. In addition, chronic exposure to sevoflurane down-regulated transcription of gonadotropin-releasing hormone (GnRH) and kisspeptin (Kiss)-1 as well as its receptor GPR54 in hypothalamus, attenuated GnRH receptor and LH-β mRNA levels, but increased FSH-β mRNA in pituitary gland, and enhanced mRNA of LH receptor and FSH receptor, but decreased INH-α and INH-βA mRNA levels in testes. Sevoflurane induces disorders of spermatogenesis and causes testicular injury. The underlying mechanism may be related to the imbalance of sex hormones in the hypothalamic-pituitary-gonadal axis.
研究七氟醚对雄性大鼠生殖功能的影响及其主要作用机制。将 40 只成年雄性 Sprague-Dawley 大鼠分为 4 组,分别暴露于 0、50、300 和 1800ppm 的七氟醚中。15 天后,采用酶联免疫吸附试验检测血清性激素和炎症因子水平。取左侧睾丸进行常规组织病理学检查和 TUNEL 染色。右睾丸用于精子生成,每天评估精子计数。采用 Johnsen 评分对生精进行分类。采用实时定量聚合酶链反应(qRT-PCR)分析下丘脑-垂体-性腺轴相关基因的表达。七氟醚暴露增加了血清促卵泡激素(FSH)、黄体生成素(LH)、肿瘤坏死因子-α(TNF-α)和单核细胞趋化蛋白 1(MCP-1)的水平,降低了血清睾酮(T)的含量,减少了睾丸精子浓度、每日精子生成量和 Johnsen 评分,并以剂量依赖的方式损害了输精管。此外,慢性暴露于七氟醚下调了下丘脑促性腺激素释放激素(GnRH)和 Kisspeptin(Kiss)-1及其受体 GPR54 的转录,减弱了 GnRH 受体和 LH-βmRNA 水平,但增加了垂体 FSH-βmRNA,增强了 LH 受体和 FSH 受体的 mRNA,但降低了睾丸 INH-α和 INH-βA mRNA 水平。七氟醚诱导精子发生障碍并导致睾丸损伤。其潜在机制可能与下丘脑-垂体-性腺轴性激素失衡有关。