The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice

In utero bisphenol A (BPA) exposure affects reproductive function in the
first generation (F1) of mice; however, not many studies have examined
the reproductive effects of BPA exposure on subsequent generations. In
this study, pregnant mice (F0) were orally dosed with vehicle, BPA (0.5,
20, and 50 μg/kg/day) or diethylstilbestrol (DES; 0.05 μg/kg/day) daily
from gestation day 11 until birth. F1 females were used to generate the
F2 generation, and F2 females were used to generate the F3 generation.
Breeding studies at the ages of 3, 6, and 9 months were conducted to
evaluate reproductive capacity over time. Further, studies were
conducted to evaluate pubertal onset, litter size, and percentage of
dead pups; and to calculate pregnancy rate, and mating, fertility, and
gestational indices. The results indicate that BPA exposure (0.5 and
50 μg/kg/day) significantly delayed the age at vaginal opening in the F3
generation compared to vehicle control. Both DES (0.05 μg/kg/day) and
BPA (50 μg/kg/day) significantly delayed the age at first estrus in the
F3 generation compared to vehicle control. BPA exposure reduced
gestational index in the F1 and F2 generations compared to control.
Further, BPA exposure (0.5 μg/kg/day) compromised the fertility index in
the F3 generation compared to control. Finally, in utero BPA exposure
reduced the ability of female mice to maintain pregnancies as they aged.
Collectively, these data suggest that BPA exposure affects reproductive
function in female mice and that some effects may be transgenerational
in nature.