Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.
BACKGROUND
The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood.


OBJECTIVE
We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility.


METHODS
Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays.


RESULTS
The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production.


CONCLUSIONS
Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.
Eustache
Florence
F
Service d'Histologie-Embryologie, Biologie de la Reproduction/CECOS (Centre d'Etude et de Conservation du Sperme Humain), Hôpital Cochin, Paris, France.
Mondon
Françoise
F
Canivenc-Lavier
Marie Chantal
MC
Lesaffre
Corinne
C
Fulla
Yvonne
Y
Berges
Raymond
R
Cravedi
Jean Pierre
JP
Vaiman
Daniel
D
Auger
Jacques
J
D000726:Androgen Antagonists / Q000633:toxicity; D000818:Animals; D004032:Diet; D004958:Estradiol / Q000097:blood; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D019833:Genistein / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010080:Oxazoles / Q000633:toxicity*; D048789:Phytoestrogens / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D010080:Oxazoles; D048789:Phytoestrogens; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D019833:Genistein; C025643:vinclozolin