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Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels Atanassova
N, McKinnell C, Turner KJ, Walker M, Fisher JS, Morley M, Millar
MR, Groome NP, Sharpe RM Medical
Research Council Human Reproductive Sciences Unit, Center for Reproductive
Biology, Edinburgh, Scotland, United Kingdom. Endocrinology 2000 Oct;141(10):3898-907 This study
investigated whether neonatal exposure of male rats to estrogenic
compounds altered pubertal spermatogenesis (days 18 and 25) and
whether the changes observed resulted in long-term changes in testis
size, mating, or fertility (days 90-100). Rats were treated neonatally
with a range of doses (0.01-10 microg) of diethylstilbestrol (DES;
administered on alternate days from days 2-12), a high dose of octylphenol
(OP; 2 mg administered daily from days 2-12) or bisphenol A (Bis-A;
0.5 mg administered daily from days 2-12), or vehicle, while maintained
on a standard soy-containing diet. The effect on the same parameters
of rearing control animals on a soy-free diet was also assessed
as was the effect of administering such animals genistein (4 mg/kg/day
daily from days 2-18). Testis weight, seminiferous tubule lumen
formation, the germ cell apoptotic index (apoptotic/viable germ
cell nuclear volume), and spermatocyte nuclear volume per unit Sertoli
cell nuclear volume were used to characterize pubertal spermatogenesis.
Compared with (soy-fed) controls, DES administration caused dose-dependent
retardation ofpubertal spermatogenesis on day 18, as evidenced by
decreases in testis weight, lumen formation, and spermatocyte nuclear
volume per unit Sertoli cell and elevation of the germ cell apoptotic
index. However, the two lowest doses of DES (0.1 and 0.01 microg)
significantly increased spermatocyte nuclear volume per unit Sertoli
cell. Similarly, treatment with either OP or Bis-A significantly
advanced this and some of the other aspects of pubertal spermatogenesis.
Maintenance of control animals on a soy-free diet also significantly
advanced lumen formation and spermatocyte nuclear volume per unit
Sertoli cell compared with controls fed a soy-containing diet. Administration
of genistein reversed the stimulatory effects of a soy-free diet
and significantly retarded most measures of pubertal spermatogenesis.
In general, plasma FSH levels in the treatment groups changed in
parallel to the spermatogenic changes (reduced when pubertal spermatogenesis
retarded, increased when pubertal spermatogenesis advanced). By
day 25, although the changes in FSH levels largely persisted, all
of the stimulatory effects on spermatogenesis seen on day 18 in
the various treatment groups were no longer evident. In adulthood,
testis weight was decreased dose dependently in rats treated neonatally
with DES, but only the lowest dose group (0.01 microg) showed evidence
of mating (3 of 6) and normal fertility (3 litters). Animals treated
neonatally with OP or Bis-A had normal or increased (Bis-A) testis
weights and exhibited reasonably normal mating/fertility. Animals
fed a soy-free diet had significantly larger testes than controls
fed a soy-containing diet, and this difference was confirmed in
a much larger study of more than 24 litters, which also showed a
significant decrease in plasma FSH levels and a significant increase
in body weight in the males kept on a soy-free diet. Neonatal treatment
with genistein did not alter adult testis weight, and although most
males exhibited normal mating and fertility, a minority did not
mate or were infertile. It is concluded that 1)
neonatal exposure of rats to low levels of estrogens
can advance the first wave of spermatogenesis at puberty, although
it is unclear whether this is due to direct effects of the estrogen
or to associated elevation of FSH levels; 2)
the effect of high doses of OP and Bis-A on these
processes is essentially benign; and 3)
the presence or absence of soy or genistein in the
diet has significant short-term (pubertal spermatogenesis) and long-term
(body weight, testis size, FSH levels, and possibly mating) effects
on males. Quotes from
the paper |