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
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 of pubertal 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
- 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;
- the effect of high doses of OP and Bis-A on these processes is
essentially benign; and
- 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
"As the dose of genistein administered in our studies was
nominally based on the total phytoestrogen exposure of human infants
fed a 100% soy-formula milk diet, our findings reinforce the conclusion
from this study that such a diet is likely to have biological
effects"
"... our finding that the continuous presence of soy in the diet
retards spermatogenic development and results in lifelong alterations
in body weight, testis weight and FSH levels does have significant
implications for all studies of male reproductive development and
function."
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