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Comment |
Characterization of FOXO1, 3 and 4 transcription factors in ovaries of fetal, prepubertal and adult rhesus macaques. Ting AY et al. (2017) The phosphoinositide 3-kinase/AKT signaling pathway negatively regulates follicle activation via the forkhead box O (FOXO) transcription factor in rodents. FOXO3 knockout mice exhibit global activation of primordial follicles leading to early depletion of ovarian follicles and subsequent infertility. Whether a similar mechanism for follicle activation exists in the primate ovary is unclear. In the current study, protein localization of FOXO1, 3 and 4 as well as their upstream regulator, AKT/p-AKT, were examined in rhesus macaque ovaries of 3 developmental stages: fetal, prepubertal and adult. FOXO1 protein is expressed in granulosa cells of fetal, prepubertal and adult ovaries. FOXO3 is distributed sparsely in the mitotically active germ cells, but its expression decreases following follicle formation in the macaque fetal ovary. In addition, FOXO3 is seldom with inter-animal variation in the prepubertal ovary and is absent in the adult ovary. FOXO4 is nondetectable in fetal ovaries, although it is expressed in some theca cells of antral follicles and some stromal cells in prepubertal and adult ovaries. Our results suggest that the regulation and/or function of FOXO3 in the primate primordial follicle may differ than that of the rodent. Nevertheless, AKT/p-AKT is expressed in macaque primordial oocytes, suggesting that similar upstream events, but different downstream effects may regulate primordial follicle activation in nonhuman primates compared to rodents. Elucidation of the mechanism responsible for follicle activation in primates will be crucial for understanding primary ovarian insufficiency, improving female fertility, and applying techniques for in vitro maturation of follicles for fertility preservation in cancer survivors.//////////////////
FOXO1, FOXO3, AND FOXO4 are differently expressed during mouse oocyte maturation and preimplantation embryo development. Kuscu N et al. (2015) Preimplantation embryo development is affected by its environment. FoxO transcription factors are regulated by PI3K/Akt signaling pathway that essentially supports growth and development. FoxO transcription factors are at the interface of crucial cellular processes, orchestrating programs of gene expression that regulate apoptosis, cell-cycle arrest, oxidative stress resistance, DNA repair, glucose metabolism, and differentiation. In the presence of growth factors, FoxO transcription factors are localized in the cytoplasm, whereas under stress conditions they move to the nucleus and trigger transcriptional activities of their target genes. The aim of the present study is to investigate whether FoxO transcription factors are present during in vivo oocyte maturation and preimplantation embryo development. Presence and localizations of FoxO1, FoxO3 and FoxO4 proteins have been determined with immunofluorescence staining. Our results have confirmed that FoxO1, FoxO3 and FoxO4 proteins are differentially expressed in prophase I, metaphase I, metaphase II oocytes, as well as in fertilized oocyte, 2-cell embryo, 4-cell embryo, 8-cell embryo, morula, and blastocyst. FoxOs translocate to nucleus in embryos with developmental delay. Our findings indicate that FoxO transcription factors are present during both oocyte and embryo in vivo maturation and provide fundamental knowledge that FoxOs may regulate in vitro embryo development under stress conditions.//////////////////
Richards JS, et al 2002 reported the expression of FKHR, FKHRL1, and AFX Genes in the Rodent
Ovary and Evidence for Regulation by IGF-I, Estrogen, and the
Gonadotropins.
This study
was undertaken to determine if during ovarian follicular development FSH regulates putative targets of PKB and Sgk,
namely specific Forkhead transcription factor family members. Using in vivo and in vitro mouse and rat models, the authors show 1)
that FKHR [Forkhead homolog of rhabdomysarcoma = Forkhead box binding protein (Foxo1), FKHRL1 (Forkhead-like
protein-1 = Foxo3), and AFX (a Forkhead transcription factor = Foxo4); all defined according to the Human and Mouse
Gene Nomenclature Committee) are expressed in the rodent ovary and 2) that FSH regulates transcription of the FKHR gene
as well as phosphorylation of FKHR protein.
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Mutations |
1 mutations
Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Expression of forkhead transcription factors in human granulosa cells. Pisarska MD et al. Members of the forkhead box O1 (FOXO) family of transcription factors are expressed in granulosa cells during various stages of follicle development, and evidence from rodent and other , we show that FOXO1, FOXO3, and FOXO4 are expressed in human luteinized mural granulosa cells, which may suggest that these transcription factors are also involved in human folliculogenesis and luteinization.
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