title: The negative effects of chronic exposure to isoflurane on spermatogenesis via breaking the hypothalamus-pituitary-gonadal equilibrium.
abstract: 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.
authors.affiliation: a Department of Anesthesiology , Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College , Yantai , China .
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Ding
authors.affiliation: a Department of Anesthesiology , Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College , Yantai , China .
authors.forename: Jianhong
authors.initials: J
authors.lastname: Yu
authors.affiliation: b Department of Anesthesiology , Yantai Affiliated Hospital of Binzhou Medical University , Yantai , China , and .
authors.forename: Pingping
authors.initials: P
authors.lastname: Qu
authors.affiliation: c Department of Anesthesiology , Qingdao Haici Medical Group , Qingdao , China.
authors.forename: Piliang
authors.initials: P
authors.lastname: Ma
authors.affiliation: a Department of Anesthesiology , Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College , Yantai , China .
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007530:Isoflurane
keywords: GnRH; HPG axis; Kisspeptin-GPR54; inhalation anesthetic; spermatogenesis