Ovary

Developmental Regulation of Follicle Stimulating Hormone Receptor Messenger RNA Expression in the Baboon Fetal Ovary

Abstract

In the adult ovary, pituitary FSH via interaction with its receptor (FSHR) is required for follicular maturation and granulosa cell development. In human and non human primates, the pool of follicles available for adult ovarian function is established in utero. However, our understanding of the ontogeny and developmental regulation of FSHR in the ovary of the primate fetus is incomplete. Therefore, we determined whether the baboon fetal ovary expressed the full-length FSHR mRNA transcript and whether levels were developmentally regulated. Fetal ovaries were obtained at mid (day 100) and late (days 165) gestation (term = day 184) from untreated baboons and on day 165 from baboons in which fetal estrogen levels were either decreased by >95% by treatment with the aromatase inhibitor CGS 20267 or restored to 30% of normal by treatment with CGS 20267 plus estradiol benzoate administered sc to the mother on days 100-164. The full-length 2088-bp FSHR mRNA transcript was expressed in ovaries of adult and fetal baboons untreated or treated with CGS 20267 or CGS 20267 and estrogen. FSHR mRNA levels (ratio to 18S rRNA), quantified by reverse transcription-polymerase chain reaction, were increased (P < 0.05) 2-fold between mid (0.34 ± 0.06) and late gestation (0.76 ± 0.07), an increase prevented (P < 0.05) in estrogen- depleted baboons (0.44 ± 0.10) and partially restored by treatment with CGS 20267 and estrogen (0.58 & [plusmn] 0.16). We previously showed that the number of follicles/0.33mm² in fetal ovaries of untreated baboons in late gestation was reduced 50% by treatment with CGS 20267 and restored to normal in baboons treated with CGS 20267 and estrogen. Thus, when corrected for the number of follicles/0.33mm², FSHR mRNA levels were similar in fetal ovaries of baboon untreated (0.010 ± 0.001) or treated with CGS 20267 (0.009 ± 0.002) or CGS 20267 and estrogen (0.007 ± 0.003). We conclude that estrogen plays a major role in regulating ovarian FSHR mRNA expression in the primate fetus and that the developmental increase in FSHR mRNA levels reflects the estrogen-dependent increase in folliculogenesis (i.e. increased number of granulosa cells and oocytes).