NCBI Summary:
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor that may regulate gene expression, morphogenesis, and differentiation. More specifically, it may function in fertility, embryo viability, and regulation of hematopoietic lineage commitment. Alternatively spliced transcript variants encoding different isoforms have been described.
General function
DNA binding, Transcription factor
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Cellular localization
Nuclear
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Ovarian function
Oogenesis
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cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles. Huntriss J et al. Nobox is a homeobox gene that is preferentially expressed in the oocytes and is essential for folliculogenesis and the regulation of oocyte-specific gene expression in the mouse. The likely human homologue has been identified in silico but has not as yet been confirmed experimentally. Here, we present the first cDNA cloning and transcript expression analysis of the human NOBOX gene. Using RT-PCR, we reveal that expression within adult human tissues is limited to the ovary, testis and pancreas. Expression within the ovary is oocyte specific, with expression observed from the primordial stage ovarian follicle through to the metaphase II (MII) oocyte. In complementary studies, we reveal dynamic expression profiles of 14 additional homeobox genes throughout human oogenesis and early development. The expression of HOXA10 is restricted to primordial and early primary follicles. HOXB7 is expressed from primordial and early primary stage follicles through to germinal vesicle (GV) oocytes. Gastrulation brain homeobox 1 (GBX1) and HOXA7 genes are homeobox markers preferentially expressed by GV oocytes. HOXA1 and HEX are homeobox markers preferentially expressed by MII oocytes. In summary, the homeobox gene transcripts that are detected in ovarian follicles and oocytes are distinct from those expressed in human blastocysts (HOXB4, CDX2 and HOXC9) and granulosa cells (HOXC9, HOXC8, HOXC6, HOXA7, HOXA5 and HOXA4).
Expression regulated by
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Ovarian localization
Oocyte, Granulosa, Luteal cells
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HOXA10 expression is decreased by testosterone in luteinized granulosa cells in vitro. He H et al. Polycystic ovary syndrome (PCOS) is perhaps the most prevalent endocrine disorder in women of reproductive age, characterized by elevated levels of circulating androgens or clinical manifestations of androgen excess. The specific cytokine profile of PCOS patients is probably related to the lower implantation rate, since follicular fluid appears to function as an embryotrophic agent. For a better understanding of the local regulation of human follicles, the present study investigated the protein expression levels and cellular localization of HOXA10 in granulosa cells (GCs) from women with normal ovarian function undergoing IVF due to their husbands suffering from azoospermia. We demonstrated by immunohistochemical studies that the expression of HOXA10 was mainly localized in the cytoplasm of GCs. Our data indicate that these alterations were associated with changes in the expression of ovarian transcription factors of HOXA10. GC dose-responsive decreases in HOXA10 protein were observed in response to physiological or supraphysiological concentrations (10-4 to 10-7M) of testosterone. These data reveal that testosterone may be involved in HOXA10 gene regulation in GCs. Decreased HOXA10 expression in GCs treated with testosterone suggest that this androgen is responsible for the decreased expression of HOXA10 in PCOS patients.