Developmental regulation of the expression of the transferrin receptor and Ki67 in oocytes of the baboon fetal ovary by estrogen.

We previously showed that estrogen regulates baboon fetal ovarian follicle development and oocyte integrity. Because iron incorporated into cells by the transferrin receptor is essential for cell/nuclear function, we determined whether fetal oocyte expression of transferrin receptor and the nuclear protein Ki67 were developmentally regulated by estrogen and associated with DNA integrity/fragmentation. Transferrin-receptor expression was minimal at midgestation and abundant in late gestation and localized to the cytoplasm and surface of oocytes of primordial follicles. Expression of transferrin receptor, however, was negligible in oocytes in fetuses in which serum estradiol-17beta levels were suppressed (>95%) by daily maternal treatment between mid- and late gestation with the aromatase inhibitor letrozole and partially restored by treatment with letrozole and estradiol benzoate. Ki67 was localized to pregranulosa and germ cells at midgestation and throughout the oocyte nucleus in late gestation in estrogen-replete fetuses. In contrast, in estrogen-suppressed fetuses, Ki67 was localized to a limited number of foci around the oocyte nucleus. Apoptosis detected in pregranulosa and germ cells at midgestation was not observed in late gestation in estrogen-replete/-suppressed fetuses. We conclude that estrogen regulates fetal oocyte transferrin-receptor expression and that inhibition of receptor development is associated with alterations in Ki67 expression by the oocyte but not apoptosis. Collectively, these results and our previous studies further define the essential role of estrogen in regulating development of follicles comprised of healthy oocytes by the baboon fetal ovary.