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Transcription factor GATA-4 has been suggested to have a role in mammalian gonadogenesis, e.g., through activation of the Mullerian-inhibiting substance (MIS) gene expression. Although the expression of GATA-4 during gonadogenesis has been elucidated in detail, very little is known about FOG-2, an essential cofactor for GATA-4, in ovarian development. We explored in detail the expression of FOG-2 and GATA-4 in the fetal and postnatal mouse ovary and in the fetal testis using Northern blotting, RNA in situ hybridization, and immunohistochemistry. GATA-4 and FOG-2 are evident in the bipotential urogenital ridge, and their expression persists in the fetal mouse ovary; this result is different from earlier reports of GATA-4 downregulation in the fetal ovary. In contrast to ovary, FOG-2 expression is lost in the fetal Sertoli cells along with the formation of the testicular cords, leading to the hypothesis that FOG-2 has a specific role in the fetal ovaries counteracting the transactivation of the MIS gene by GATA-4. In vitro transfection assays verified that FOG-2 is able to repress the effect of GATA-4 on MIS transactivation in granulosa cells. In postnatal ovary, granulosa cells of growing follicles express FOG-2, partially overlapping with the expression of MIS. These data suggest an important role for FOG-2 and the GATA transcription factors in the developing ovary.

Recently, two studies have reported an association between the alpha2-macroglobulin gene on chromosome 12 and late-onset Alzheimer's disease, whereas others have not been able to replicate these findings. By using a prospective population-based study, we have investigated the relation between two polymorphisms in this gene with the presence of the disease and also with the extent of pathological changes in the cerebral cortex. The Vantaa 85+ Study includes all 601 persons, at least 85 years of age, who were living in Vantaa, Finland, on April 1, 1991. The neocortical beta-amyloid protein load and the number of neurofibrillary tangles were determined on tissue sections by using methenamine silver staining and a modified Bielschowsky staining, respectively. The A/A genotype in exon 24 of the alpha2-macroglobulin gene was associated with neuropathologically defined diagnosis of Alzheimer's disease according to the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria and with an increase in the neocortical beta-amyloid protein load. The effect of this association was stronger in the apolipoprotein E epsilon4-negative group. Therefore, genetic variability in the alpha2-macroglobulin gene is a risk factor associated with neuropathologically defined Alzheimer's disease in our population, as well as with the extent of neocortical beta-amyloid protein deposition.

Transcription factor GATA-4 has been suggested to have a role in mammalian gonadogenesis, e.g., through activation of the Müllerian-inhibiting substance (MIS) gene expression. Although the expression of GATA-4 during gonadogenesis has been elucidated in detail, very little is known about FOG-2, an essential cofactor for GATA-4, in ovarian development. We explored in detail the expression of FOG-2 and GATA-4 in the fetal and postnatal mouse ovary and in the fetal testis using Northern blotting, RNA in situ hybridization, and immunohistochemistry. GATA-4 and FOG-2 are evident in the bipotential urogenital ridge, and their expression persists in the fetal mouse ovary; this result is different from earlier reports of GATA-4 downregulation in the fetal ovary. In contrast to ovary, FOG-2 expression is lost in the fetal Sertoli cells along with the formation of the testicular cords, leading to the hypothesis that FOG-2 has a specific role in the fetal ovaries counteracting the transactivation of the MIS gene by GATA-4. In vitro transfection assays verified that FOG-2 is able to repress the effect of GATA-4 on MIS transactivation in granulosa cells. In postnatal ovary, granulosa cells of growing follicles express FOG-2, partially overlapping with the expression of MIS. These data suggest an important role for FOG-2 and the GATA transcription factors in the developing ovary.