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Inhal Toxicol. 2019 Sep - Oct;31(11-12):392-398. doi: 10.1080/08958378.2019.1698677. Epub 2019 Dec 5.

Effects of sevoflurane on reproductive function of male rats and its main mechanism of action.

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Department of Pain, Linzi District People's Hospital, Zibo, China.
Department of Obstetrics, Yantaishan Hospital, Yantai, China.
Department of Anesthesiology, Yantaishan Hospital, Yantai, China.
Department of Anesthesiology, The Second Hospital of Shandong University, Jinan, China.
Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
Department of Pain, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
Department of Anesthesiology, Yeda Hospital, Yantai, China.


Objective: To study the effects of sevoflurane on reproductive function and its main mechanism of action in male rats.Materials and methods: 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).Results: 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.Discussion and conclusions: 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.


Sevoflurane; hypothalamic-pituitary-gonadal axis; male rats; reproductive function; sperm

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