Prenatal diethylstilbestrol exposure in the mouse: effects on ovarian histology and steroidogenesis in vitro.

The effect of prenatal diethylstilbestrol (DES) exposure on ovarian morphology and steroid production in vitro was evaluated in the mouse. Pregnant mice were injected with 100 micrograms DES per kg maternal body weight on Days 9 to 16 of gestation and the female offspring sacrificed from 3 to 14 months of age. Ovaries of DES-exposed animals weighed significantly less than controls at 3 months of age (9.4 +/- 0.79 mg vs. 17.54 +/- 0.69 mg, mean +/- SEM). Histologically, the DES animals had an apparent increase in the size of the interstitial compartment with cells showing uniform vacuolization and tubular architecture. In addition, the lipid content of the interstitial compartment, as assessed by oil-red-O staining, was markedly increased in the treated animals as compared to controls and corresponded to the vacuolization. Ovarian steroidogenesis in vitro was determined by excising ovaries of animals from 3 to 14 months of age, placing them in tissue culture for 24 h, and measuring media steroids by radioimmunoassay. Estrogen, progesterone and testosterone production per mg of tissue was increased in DES-exposed animals at all ages studied. To correct for changes in the relative sizes of the ovarian compartments secondary to DES exposure, steroid production was calculated on a "per ovary" basis. Only testosterone production remained elevated "per ovary" in the DES-exposed animals which is consistent with androgens being the primary secretory products of the enlarged interstitial compartment. These data indicate that in the mouse, prenatal DES exposure is associated with an enlargement of the ovarian interstitial compartment, increased lipid content of the individual interstitial cells, and increased interstitial compartment testosterone production in vitro throughout the reproductive life span of the animal.