Estradiol synthesis by fetal monkey ovaries correlates with antral follicle formation

We compared the morphology of ovaries from fetal rhesus monkeys at two different stages of gestation with the ability of ovarian tissue to synthesize androgens and estrogens in vitro. Ovaries collected between 80 and 104 days of gestation contained single-layered primordial follicles but no multilayered or antral follicles. Within these ovaries we found theca-like interstitial cells which contained abundant smooth endoplasmic reticulum and lipid droplets. These ovaries produced androstenedione and dehydropiandrosterone (but not estradiol) in vitro in the absence of exogenous substrates. Ovaries collected between Days 124 and 153 of gestation, however, contained numerous, well-developed multilayered and antral follicles. The ultrastructural characteristics of the thecal and granulosa cell layers were similar to those of adult ovarian follicles. These ovaries synthesized large amounts of androstenedione, dehydroepiandrosterone, and estradiol in vitro. Identity of the estradiol was confirmed by incubating homogenates of late gestation ovaries with [14C]progesterone, by isolation of estradiol and formation of its derivative, and by recrystallization to constant specific activity. In vitro cyclic AMP synthesis was stimulated by Pergonal (luteinizing hormone [LH] + follicle stimulating hormone [FSH] ) only in ovaries which contained multilayered and antral follicles, an indication that fetal ovaries contain gonadotropin receptors during late stages of development. These data indicate that fetal ovaries of rhesus monkeys attain the capacity for de novo estrogen biosynthesis and to respond to gonadotropins during late gestation, when multilayered and antral follicles have developed.