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Human Fetal Ovary Development Involves the Spatiotemporal Expression of P450c17 Protein

Department of Reproductive Medicine (B.C., K.H., J.C., G.F.E.), University of California, San Diego, La Jolla, California 92093; and Universidade Federal de São Paulo (G.A.R.M.), São Paulo, Brazil 01311-940

Address all correspondence and requests for reprints to: Gregory F. Erickson, Ph.D., Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093-0633. E-mail: gerickson{at}ucsd.edu.

Objective: The purpose of this research was to characterize the spatiotemporal expression of P450c17 in the human fetal ovary.

Design: P450c17 protein was visualized in sections of control and anencephalic ovaries using immunohistochemistry.

Subjects: Subjects included control (nonanencephalic) and anencephalic human fetal ovaries during the second and third trimesters.

Results: In second-trimester control ovaries, P450c17 was highly expressed in primary interstitial cells (PIC) located between the ovigerous cords near the cortical-medullary border where meiosis and primordial follicle formation were occurring. Morphometric analysis revealed a progressive decrease in the number of PIC during the second trimester, suggesting that PIC might have a finite lifetime. Between 25 and 32 wk, relatively few cells stained positive for P450c17; however, after 33 wk, P450c17 was strongly expressed in theca interstitial cells (TIC) bordering developing follicles. Surprisingly, the TIC appeared remarkably early during folliculogenesis, e.g. as early as the primary-to-secondary transition, and exhibited notable hyperplasia throughout preantral and early antral follicle growth. Owing to large numbers of developing preantral follicles, the third trimester was characterized by an increased abundance of P450c17-positive TIC. During this time period, P450c17 was strongly expressed in the hilus interstitial cells juxtaposed to the rete ovarii. Studies of ovaries of anencephalic fetuses revealed a similar spatiotemporal pattern of P450c17 expression in the PIC, TIC, and hilus interstitial cells, consistent with the possibility that pituitary hormones may not be involved in P450c17 expression in fetal ovaries.

Conclusion: We identified three different classes of P450c17-expressing interstitial cells in the human fetal ovary, each having a different spatiotemporal pattern of P450c17 expression and, presumably, a different set of physiological functions.

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