title: Human testis steroidogenesis is inhibited by phthalates.
abstract: BACKGROUND
  Phthalic acid esters are widely used in the manufacture of plastics. Numerous studies have shown that these phthalates impair testicular testosterone production in the rat. However, the scarce and contradictory data concerning humans have cast doubt over whether these compounds are also anti-androgenic in man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human testis and a human cell line.
  
  
  METHODS
  Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with DEHP or MEHP. The effects of ketoconazole, used as a reference molecule, were also assessed.
  
  
  RESULTS
  In both models, DEHP and MEHP significantly inhibited testosterone production. The effects of both phthalates appeared to be specific for steroidogenesis, as INSL3 production by Leydig cells was not altered. Furthermore, the phthalates of interest had no effect on inhibin B production by Sertoli cells or on germ cell apoptosis. As only a small fraction of the phthalates added was found in the testis explants, and as these compounds were found to be metabolized, we estimate that the anti-androgenic effects observed occurred at concentrations of phthalates that are of the same order of magnitude as exposures reported in the literature for men.
  
  
  CONCLUSIONS
  We provide the first evidence that DEHP and MEHP can inhibit testosterone production in the adult human testis. This is consistent with recent epidemiological findings of an inverse correlation between exposure to MEHP and testosterone concentrations.
authors.affiliation: Institut national de la santé et de la recherche médicale, IRSET, U1085, Campus de Beaulieu, F-35042 Rennes CEDEX, France.
authors.forename: C
authors.initials: C
authors.lastname: Desdoits-Lethimonier
authors.forename: O
authors.initials: O
authors.lastname: Albert
authors.forename: B
authors.initials: B
authors.lastname: Le Bizec
authors.forename: E
authors.initials: E
authors.lastname: Perdu
authors.forename: D
authors.initials: D
authors.lastname: Zalko
authors.forename: F
authors.initials: F
authors.lastname: Courant
authors.forename: L
authors.initials: L
authors.lastname: Lesné
authors.forename: F
authors.initials: F
authors.lastname: Guillé
authors.forename: N
authors.initials: N
authors.lastname: Dejucq-Rainsford
authors.forename: B
authors.initials: B
authors.lastname: Jégou
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity*; D006801:Humans; D007265:Inhibins / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism; D007654:Ketoconazole / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D046509:Tissue Culture Techniques
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; C422364:inhibin B; D013739:Testosterone; D007265:Inhibins; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; D007654:Ketoconazole