title: Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats.
abstract: BACKGROUND
  Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen.
  
  
  METHODS
  Thirty-two adult male rats were divided into four groups randomly: group GH, rats were fed orally with gossypol acetic acid (GA, 12.5 mg×kg(-1)×d(-1)) and desogestrel (DSG, 0.125 mg×kg(-1)×d(-1))/ethinylestradiol (EE, 0.025 mg×kg(-1)×d(-1))/testosterone undecanoate (TU, 100 mg×kg(-1)×d(-1)); group G, a single dose of GA (12.5 mg×kg(-1)×d(-1)) was given; group H, the same dosage of DSG/EE/TU as in group GH were administered; group C, rats were treated with vehicle (1% methyl cellulose) as control. Testes and epididymis were removed at 8 weeks post-treatment for evaluating their weight, volumes, volume fraction, and total volume of testicular tissue structures and the seminiferous tubule diameter using stereological assay. Sperm cell numbers and the motility of epididymal sperm were quantitated by flow cytometry and morphological methods.
  
  
  RESULTS
  Compared with group C, spermatogenesis was normal in group G and suppressed in groups H and GH. Similar changes of testicular tissue structures and sperm number were found in groups H and GH. The decreases of epididymal sperm number and motility in group GH were greater than that of the low-dose gossypol or steroid hormones alone group.
  
  
  CONCLUSIONS
  The suppression of spermatogenesis was induced by steroid hormones in the combined regimen, and the epididymis was the target organ of low-dose gossypol. Combined use of low-dose gossypol and steroid hormones played a comprehensive antifertility role in their synergistic effect on reducing the number and motility of epididymal sperm.
authors: Department of Anatomy, Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors: Qing
authors: Q
authors: Chang
authors: Zhe
authors: Z
authors: Liu
authors: Wen-Zhi
authors: WZ
authors: Ma
authors: Chang-Chun
authors: CC
authors: Hei
authors: Xin-Sheng
authors: XS
authors: Shen
authors: Xiao-Jing
authors: XJ
authors: Qian
authors: Zeng-Lu
authors: ZL
authors: Xu
mesh_terms: D000818:Animals; D017135:Desogestrel / Q000494:pharmacology; D004822:Epididymis / Q000187:drug effects; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005434:Flow Cytometry; D006072:Gossypol / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D013739:Testosterone; D004997:Ethinyl Estradiol; D017135:Desogestrel; C010792:testosterone undecanoate; D006072:Gossypol; C028178:gossypol acetic acid