Diethylstilbestrol inhibits the expression of the steroidogenic acute regulatory protein in mouse fetal testis.
This study investigated the early deleterious effects of an in-utero exposure to diethylstilbestrol (DES) on mouse testicular development. To that purpose, pregnant mice were injected daily with up to 100 microg/kg DES from 10.5 to 17.5 days postcoitum (dpc). At 18.5 dpc, testes were removed from fetuses for RNA (RT-PCR) and protein (Western blot, immunohistochemistry) analysis. Twenty-two genes were selected among which transcription factors, markers of differentiation of the different testicular cell lineages, steroidogenic enzymes and hormone receptors. The Steroidogenic Acute Regulatory (StAR) protein produced by the fetal Leydig cells was dramatically reduced in the DES-exposed testes. The P450c17 was the other gene modified following DES exposure. The alteration of these two genes is consistent with the decrease observed in the intratesticular testosterone levels, in the DES-exposed testes. Collectively, we demonstrated that DES did not alter testicular cell lineage specification but that it strongly inhibited the major function of the fetal Leydig cells.
Guyot
Romain
R
Inserm U329, Hopital Debrousse, 29 rue Soeur Bouvier, 69322 Lyon, France.
Odet
Fanny
F
Leduque
Patrick
P
Forest
Maguelone G
MG
Le Magueresse-Battistoni
Brigitte
B
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D004054:Diethylstilbestrol; D015096:3-Hydroxysteroid Dehydrogenases