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 muscolus domesticus (Y-DOM) mouse strain from Tirano (Italy) or Mus musculus poschiavinus (Y-POS) from Poschiav o (Switzerland), is placed onto the C57BL/6J (B6) inbred background, t he Y-DOM chromosome fails to induce normal testicular differentiation and instead allows development of ovaries and ovotestes in embryonic l ife. During postnatal development some hermaphroditic males become fer tile 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 s teroidogenesis. RNA was isolated from the XX and the XY ovaries at 1 t o 40 d.p.p. and subjected to RT-PCR analysis. Immunocytochemical stain ing for IGF-I was performed to identify the cell type of IGF-I peptide localization, and protein expression was examined by Western blot ana lysis. The present results indicate that the IGF-I transcript was expr essed at 1 d.p.p. in the XX ovary throughout the studied stages wherea s in the XY ovary mRNA IGF-I was not detected until 15 d.p.p. IGF-I pr otein was identified in theca cells in the whole XX control ovary, whi le in the XY ovary, strong staining for IGF-I was found in the theca c ells 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 ov ary at 11 and 26 d.p.p. compared to the XX control ovary. We propose t hat delayed expression of IGF-I in the XY mouse ovary may be responsib le for low steroid production and fertility problems in the XY sex-rev ersed adult female mouse.