title: Relationship of leptin administration with production of reactive oxygen species, sperm DNA fragmentation, sperm parameters and hormone profile in the adult rat.
abstract: OBJECTIVE
  Leptin, an adipose tissue-derived hormone, plays an important role in energy homeostasis and metabolism, and in the neuroendocrine and reproductive systems. The function of leptin in male reproduction is unclear; however, it is known to affect sex hormones, sperm motility and its parameters. Leptin induces mitochondrial superoxide production in aortic endothelia and may increase oxidative stress and abnormal sperm production in leptin-treated rats. This study aims to evaluate whether exogenous leptin affects sperm parameters, hormone profiles, and the production of reactive oxygen species (ROS) in adult rats.
  
  
  METHODS
  A total of 65 Sprague-Dawley rats were divided into three treated groups and a control group. Treated rats received daily intraperitoneal injections of 5, 10 and 30 μg/kg of leptin administered for a duration of 7, 15, and 42 days. Control rats were given 0.1 mL of 0.9 % normal saline for the same period. One day after final drug administration, we evaluated serum specimens for follicle-stimulating hormone (FSH), leutinizing hormone (LH), free testosterone (FT), and total testosterone (TT) levels. Samples from the rat epididymis were also evaluated for sperm parameters and motility characteristics by a Computer-Aided Semen Analysis (CASA) system. Samples were treated with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) and analyzed using flow cytometry and TUNEL to determine the impact of leptin administration on sperm DNA fragmentation.
  
  
  RESULTS
  According to CASA, significant differences in all sperm parameters in leptin-treated rats and their age-matched controls were detected, except for TM, ALH and BCF. Serum FSH and LH levels were significantly higher in rats that received 10 and 30 μg/kg of leptin compared to those treated with 5 μg/kg of leptin in the same group and control rats (P < 0.05). ROS and sperm DNA fragmentation was significantly higher in rats injected with 10 and 30 μg/kg of leptin for 7 and 15 days compared with rats treated with 5 μg/kg of leptin and the control group (P < 0.05) for the same time period. However, at day 42 of treatment, ROS and sperm DNA fragmentation levels significantly decreased in all groups (P < 0.05).
  
  
  CONCLUSIONS
  According to these results, leptin can possibly affect male infertility by ROS induction or hormone profile modulation.
authors.affiliation: Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, 16635-148, Tehran, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Abbasihormozi
authors.forename: Abdolhossein
authors.initials: A
authors.lastname: Shahverdi
authors.forename: Azam
authors.initials: A
authors.lastname: Kouhkan
authors.forename: Javad
authors.initials: J
authors.lastname: Cheraghi
authors.forename: Ali Asghar
authors.initials: AA
authors.lastname: Akhlaghi
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Kheimeh
mesh_terms: D000818:Animals; D053938:DNA Fragmentation / Q000187:drug effects*; D005298:Fertility / Q000502:physiology; D005640:Follicle Stimulating Hormone / Q000097:blood; D006728:Hormones / Q000097:blood*; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D012661:Semen / Q000737:chemistry; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000097:blood
chemical_list: D006728:Hormones; D020738:Leptin; D017382:Reactive Oxygen Species; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone