Hedgehog Signaling Plays a Critical Role in Directing Correct Primordial Follicle Formation in the Mouse Ovary

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The Hedgehog (HH) signaling pathway has been identified to play an essential role in cell differentiation, cell fate determination and cell proliferation in both Drosophila and mammalian models. While much is known regarding HH actions in the Drosophila ovary, its role in the developing mammalian ovary remains a mystery. In the days following birth, the mouse ovary transitions from an organ filled with ovigerous cords to one filled with primordial follicles, which are oocytes surrounded by a layer of flattened pre-granulosa epithelial cells, enclosed by a basement membrane, and associated with mesenchymal cells. The purpose of this study was to determine the role HH plays in primordial follicle formation in the mouse ovary. HH signaling was blocked by injecting cyclopamine, a plant alkaloid known to inhibit HH signaling, on days 0, 1, 2 and 3 after birth. Immunohistochemistry using an antibody for laminin, a common basement membrane protein, revealed a significantly higher number of discontinuous basement membranes around primordial follicles in ovaries extracted from cyclopamine-treated mice. H&E staining revealed a significantly lower ratio of mesenchymal cells to oocytes in ovaries from cyclopamine-treated mice, as compared to controls. The reduced HH signaling in this study is thought to have disrupted proper ovigerous cord breakdown and interfered with normal cell communication among oocytes, epithelial cells and mesenchymal cells, suggesting that the HH signaling pathway does play a critical role in directing correct primordial follicle development. This study provides valuable insight into the role HH plays in the developing mouse ovary.
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hedgehog; primordial follicles; ovary; follicle development
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