Reduced GLUT1 expression in Igf1-I- null oocytes and follicles

Granulosa cells provide nutritional and trophic support for growing oocytes in ovarian follicles. The granulosa cells closest to the oocyte produce ab undant insulin-like growth factor 1 (IGF1) and the IGF1 receptor is highly expressed by oocytes, suggesting that granulosa-derived IGF1 may have troph ic effects on oocyte growth and development. To investigate this possibilit y, in the present study we used in situ hybridization and immunohistochemis try to examine glucose transporter (GLUTs 1, 3 & 4) expression in follicles from pre-pubertal Igf1-/- and littermate wildtype (wt) mice. Pre-pubertal mice were used for this study because the Igf1 null mice do not mature sexu ally. GLUT1 mRNA and immunoreactivity were most abundant in oocytes and in granulosa cells immediately surrounding the oocyte. Expression of this tran sporter was significantly reduced in Igf1 null oocytes and granulosa cells and was restored by exogenous IGF1 treatment to wt levels. These effects on GLUT expression were significant at both the mRNA and immunoreactive prote in levels. Oestrogen treatment significantly increased GLUT1 levels in oocy tes and granulosa from both wt and Igf1-/-, although the latter were still significantly lower than wt. Oocyte glycogen stores, determined by PAS stai ning, did not appear different in Igf1-/- and wt mice. GLUT3 was expressed in thecal cells surrounding growing follicles and was n ot appreciably different in Igf1 null compared with wt ovaries. GLUT4 expre ssion was not detected in the prepubertal mouse ovary. Together with observ ations from previous studies showing that ovulation is blocked in Igf1 null mice, the present data suggest that IGF1's augmentation of granulosal and oocyte GLUT1 expression may be essential for oocyte maturation and successf ul ovulation. (C) 2000 Harcourt Publishers Ltd.