Details

Autor(en) / Beteiligte

• SHARPE, R. M
• ATANASSOVA, N
• SAUNDERS, P. T. K
• MCKINNELL, C
• PARTE, P
• TURNER, K. J
• FISHER, J. S
• KERR, J. B
• GROOME, N. P
• MACPHERSON, S
• MILLAR, M. R

Titel

Abnormalities in Functional Development of the Sertoli Cells in Rats Treated Neonatally with Diethylstilbestrol: A Possible Role for Estrogens in Sertoli Cell Development

Ist Teil von

• Biology of reproduction, 1998-11, Vol.59 (5), p.1084-1094

Ort / Verlag

Madison, WI: Society for the Study of Reproduction

Erscheinungsjahr

1998

Quelle

MEDLINE

Beschreibungen/Notizen

• Diethylstilbestrol (DES) was administered neonatally (Days 2–12; 10 μg on alternate days) to rats, and developmental changes in Sertoli cell function were evaluated at 18, 25, and 35 days of age and compared to those observed in rats administered a GnRH antagonist (GnRHa; Days 2 and 5; 10 mg/kg) or a vehicle (controls). DES and GnRHa treatments resulted in similar reductions in both Sertoli cell numbers (40% for DES, 48% for GnRHa) and suppression of testicular growth at 18 and 25 days, though by 35 days the suppression was more pronounced ( p < 0.001) in DES-treated animals. Plasma FSH levels were suppressed markedly at 18 and 25 days, but not at 35 days, in GnRHa-treated rats, whereas in DES-treated rats the FSH levels were suppressed significantly only at 35 days. Both treatments suppressed plasma levels of inhibin B, though this was more pronounced ( p < 0.05) in DES- than in GnRHa-treated rats. In controls, Sertoli cell immunoexpression of inhibin α, sulfated glycoprotein-1 (SGP-1), and androgen receptor (AR) increased in intensity and changed to an adult, stage-dependent pattern by 25 days. In GnRHa-treated rats these changes were reduced in intensity but were similar to those in controls at 35 days. In DES-treated rats, the increase in intensity and stage-dependent pattern of immunoexpression of inhibin α, SGP-1, and AR were virtually absent at 25 days but were present by 35 days. Germ cell volume per Sertoli cell was reduced in GnRHa- and DES-treated rats compared with controls at 18 and 25 days but was significantly greater ( p < 0.001) in DES- than in GnRHa-treated rats at 35 days. The proportion of apoptotic to viable germ cells was increased ( p < 0.01) in GnRHa- and DES-treated rats compared with controls at 18 and 25 days; but at 35 days, values in GnRHa-treated rats had declined to control values whereas those for DES-treated rats remained 10-fold elevated ( p < 0.001). In adulthood, testis weight and daily sperm production were reduced by 43% and 44%, respectively, in GnRHa-treated rats, but spermatogenesis was grossly normal. Comparable changes were observed in ∼25% of DES-treated rats, but the majority exhibited > 60% reduction in testis weight with many Sertoli cell-only tubules and very low daily sperm production. Taken together, these data are interpreted as providing evidence for direct modulation of Sertoli cell (maturational) development by DES.