Dichlorodiphenyltrichloroethane impairs follicle-stimulating hormone receptor-mediated signaling in rat Sertoli cells.
Any toxicant that affects Sertoli cell development can potentially disturb male fertility. So far, the effects of organochlorine compounds have been poorly investigated in male. Here, we studied the effects of dichlorodiphenyltrichloroethane (DDT), an organochloride pesticide, on Sertoli cells. DDT inhibited the cAMP response to follicle-stimulating hormone (FSH), the major endocrine control of Sertoli cell development, and to a beta2-agonist, isoproterenol. DDT exposure decreased the level of FSH binding sites. Direct adenylyl cyclase activation by Forskolin was unaltered by DDT, while the activation of Galphas by cholera toxin was decreased by DDT. The DDT inhibitory effect on the FSH response was also observed in Ser W3 cells, a Sertoli cell-derived immortalized cell line. All these effects were reproduced by the lipophilic aromatic bisphenol A but not by structurally unrelated CisPlatin. In conclusion, these results are a first step in understanding the molecular basis of DDT deleterious effects in spermatogenesis.
Bernard
Laure
L
Physiologie de la Reproduction et des Comportements, UMR 6175, Institut National de la Recherche Agronomique, Centre National Pour la Recherche Scientifique, Université de Tours, Haras Nationaux, Nouzilly, France.
Martinat
Nadine
N
Lécureuil
Charlotte
C
Crépieux
Pascale
P
Reiter
Eric
E
Tilloy-Ellul
Anne
A
Chevalier
Stéphane
S
Guillou
Florian
F
D000818:Animals; D001559:Benzhydryl Compounds; D002461:Cell Line, Transformed; D002772:Cholera Toxin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003634:DDT / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010575:Pesticides / Q000633:toxicity*; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D011962:Receptors, FSH / Q000187:drug effects* / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002772:Cholera Toxin; D002945:Cisplatin; D000242:Cyclic AMP; D003634:DDT; D007545:Isoproterenol; D010575:Pesticides; D010636:Phenols; D011962:Receptors, FSH; C006780:bisphenol A; D000098826:Bisphenol A Compounds