Delayed expression of the insulin-like growth factor I (IGF-I) gene in the XY sex-reversed female mouse ovary.

When the Y chromosome of Mus musculus domesticus (YDOM) mouse strain from Tirano (Italy) or Mus musculus poschiavinus (YPOS) from Poschiavo (Switzerland), is placed onto the C57BL/6J (B6) inbred background, the YDOM chromosome fails to induce normal testicular differentiation and instead allows development of ovaries and ovotestes in embryonic life. During postnatal development some hermaphroditic males become fertile whereas the XY females lack normal estrus cyclicity, produce low levels of gonadal steroids and cannot carry pregnancy to term. Here we studied the transcription of the IGF-I gene known to be involved in steroidogenesis. RNA was isolated from the XX and the XY ovaries at 1 to 40 d.p.p. and subjected to RT-PCR analysis. Immunocytochemical staining for IGF-I was performed to identify the cell type of IGF-I peptide localization, and protein expression was examined by Western blot analysis. The present results indicate that the IGF-I transcript was expressed at 1 d.p.p. in the XX ovary throughout the studied stages whereas in the XY ovary mRNA IGF-I was not detected until 15 d.p.p. IGF-I protein was identified in theca cells in the whole XX control ovary, while in the XY ovary, strong staining for IGF-I was found in the theca cells of the cortex. Faint staining was also seen around the medullary sterile cords. Western blot analysis showed normal onset in the XX and the XY ovary, but a different staining pattern for IGF-I in the XY ovary at 11 and 26 d.p.p. compared to the XX control ovary. We propose that delayed expression of IGF-I in the XY mouse ovary may be responsible for low steroid production and fertility problems in the XY sex-reversed adult female mouse.