title: Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet.
abstract: OBJECTIVE
  The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL.
  
  
  RESULTS
  Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P < 0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P < 0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P < 0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P < 0.05).
  
  
  CONCLUSIONS
  HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Yan
authors.forename: Yang
authors.initials: Y
authors.lastname: Mu
authors.forename: Nan
authors.initials: N
authors.lastname: Yu
authors.forename: Tai-lang
authors.initials: TL
authors.lastname: Yi
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiang-li
authors.initials: XL
authors.lastname: Pang
authors.forename: Dan
authors.initials: D
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009765:Obesity / Q000209:etiology* / Q000503:physiopathology; D020011:Protective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*
chemical_list: D007004:Hypoglycemic Agents; D020011:Protective Agents; D008687:Metformin