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DEVELOPMENTAL REGULATION OF BABOON FETAL OVARIAN MATURATION BY ESTROGEN.
Zachos, Nicholas1, Billiar, Reinhart1, Albrecht, Eugene2, Pepe, Gerald1, 1 2
ABSTRACT- Development of the primate ovary occurs in utero and involves envelopment of fetal oogonia by granulosa. Although folliculogenesis is initiated at midgestation, continues through fetal life, and results at birth in an ovary comprised of follicles that serve as the adult ovulatory pool, regulation of this process is unknown. During baboon pregnancy, placental secretion of estrogen into the fetus increases and the fetal ovary expresses estrogen receptors and . To determine whether estrogen regulates ovarian development, fetal ovaries were obtained on day 165 (term = d184) from baboons untreated (n=5) or treated on d100-165 with the aromatase inhibitor CGS 20267 alone (2 mg/d; n=4) or with estradiol benzoate (2 mg each/d; n=5) and the number of follicles and interfollicular mesenchymal nests in areas (0.33 mm2) of the outer (O) and inner (I) cortex quantified. Fetal serum estradiol levels were decreased by 95% (P<0.01) by CGS 20267 and restored by CGS 20267 and estrogen. Although fetal ovarian weight was unaltered, the number of follicles in untreated baboons (I = 59 ± 2; O = 95 ± 2) was decreased (P<0.05) in estrogen-deprived animals (I = 26 ± 1; O = 62 ± 3) and restored (P<0.05) by CGS 20267 and estrogen (I = 65 ± 5; O = 97 ± 6). Moreover, the number of intact follicles was 3-fold lower (P<0.05) in CGS 20267-treated baboons (3 ± 1) than in untreated or CGS 20267-estrogen treated animals. In contrast, the number of interfollicular nests (I = 6 ± 1; O = 3 ± 1) was increased 2-fold (P<0.05) in estrogen-suppressed animals and restored (P<0.05) by CGS 20267 and estrogen. Finally, the number of primary-like follicles in untreated baboons (0.6 ± 0.1) was increased (P<0.05) by CGS 20267 (2.3 ± 0.2); an increase attenuated by CGS 20267 and estrogen (1.5 ± 0.1). In summary, fetal ovarian development was significantly altered in baboons in which estrogen was suppressed during the second half of gestation and restored to normal by estradiol. We conclude that estrogen plays an integral role in regulating primate fetal ovarian development, a process that may impact on fertility and ovarian function in adulthood. Supported by NIH NICHD HD 36207 Specialized Cooperative Centers Program in Reproduction Research.
KEY WORDS: fetal ovary, baboon, estrogen, follicle development
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