title: Modified expression of several sperm proteins after chronic exposure to the antiandrogenic compound vinclozolin.
abstract: Little is known about the molecular impact of in vivo exposure to endocrine disruptors (EDs) on sperm structures and functions. We recently reported that the lifelong exposure of rats to the antiandrogenic compound vinclozolin results in low epididymal weight, changes in sperm kinematic parameters, and immature sperm chromatin condensation, together with the impairment of several fertility end points. These results led us to focus specifically on possible molecular abnormalities in sperm. Sperm samples were recovered from the frozen epididymides of rats exposed during the previous study. The proteins present in the samples from six exposed and six control rats were analyzed in pairs, by two-dimensional fluorescence difference gel electrophoresis, to investigate possible exposure-induced changes to sperm protein profiles. Twelve proteins, from the 380 matched spots observed in at least five gels, were present in larger or smaller amounts after vinclozolin exposure. These proteins were identified by mass spectrometry, and several are known to play a crucial role in the sperm fertilizing ability, among which, two mitochondrial enzymes, malate dehydrogenase 2 and aldehyde dehydrogenase (both of which were present in smaller amounts after treatment) and A-kinase anchor protein 4 (larger amounts of precursor after treatment). Finally, Ingenuity Pathway Analysis revealed highly significant interactions between proteins over- and underexpressed after treatment. This is the first study to show an association between in vivo exposure to an ED and changes to the sperm protein profile. These modifications may be at least partly responsible for the reproductive abnormalities and impaired fertility recently reported in this rat model of vinclozolin exposure.
authors.affiliation: Service d'Histologie-Embryologie, Biologie de la Reproduction/CECOS, 75014 Paris, France. jacques.auger@cch.aphp.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Auger
authors.forename: Florence
authors.initials: F
authors.lastname: Eustache
authors.forename: Paula
authors.initials: P
authors.lastname: Maceiras
authors.forename: Cédric
authors.initials: C
authors.lastname: Broussard
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.forename: Corinne
authors.initials: C
authors.lastname: Lesaffre
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.forename: Luc
authors.initials: L
authors.lastname: Camoin
authors.forename: Jana
authors.initials: J
authors.lastname: Auer
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D010080:Oxazoles / Q000633:toxicity*; D010449:Peptide Mapping; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013094:Spermatozoa / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D010080:Oxazoles; D011506:Proteins; D008291:Malate Dehydrogenase; D000444:Aldehyde Dehydrogenase; C025643:vinclozolin