JY-1, an oocyte-specific gene, regulates granulosa cell function and early embryonic development in cattle

Laboratory of Mammalian Reproductive Biology and Genomics, and Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2007; 104(45):17602-7. DOI: 10.1073/pnas.0706383104
Source: PubMed


Oocyte-specific gene products play a key role in regulation of fertility in mammals. Here, we describe the discovery, molecular characterization, and function of JY-1, a bovine oocyte-expressed gene shown to regulate both function of ovarian granulosa cells and early embryogenesis in cattle and characteristics of JY-1 loci in other species. The JY-1 gene encodes for a secreted protein with multiple mRNA transcripts containing an identical ORF but differing lengths of 3' UTR. JY-1 mRNA and protein are oocyte-specific and detectable throughout folliculogenesis. Recombinant JY-1 protein regulates function of follicle-stimulating hormone-treated ovarian granulosa cells, resulting in enhanced progesterone synthesis accompanied by reduced cell numbers and estradiol production. JY-1 mRNA of maternal origin is also present in early bovine embryos, temporally regulated during the window from meiotic maturation through embryonic genome activation, and is required for blastocyst development. The JY-1 gene has three exons and is located on bovine chromosome 29. JY-1-like sequences are present on syntenic chromosomes of other vertebrate species, but lack exons 1 and 2, including the protein-coding region, suggestive of species specificity in evolution and function of this oocyte-specific gene.

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Available from: Aritro Sen, Jul 17, 2015
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    • "However, the syntenic loci do not encode for the complete JY-1 gene and lack sequences corresponding to exons 1 and 2, and thus a significant portion of the protein coding region. Therefore, Bettegowda et al. (2007) concluded that the oocyte-specific JY-1 protein is probably species specific. Incidentally, Rajput et al. (2013) recently identified expression of JY-1 in buffaloes and reported polymorphisms, including insertion of a thymine in the codifying region of exon 3 of the buffalo sequence. "
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    ABSTRACT: The JY-1 protein is oocyte specific, and is associated with folliculogenesis and early embryo development, and thus influences the chance of pregnancy. It was the first protein of maternal origin to be described for a single ovulating species, namely cattle. JY-1-like sequences corresponding to 3’ coding and the untranslated region have been reported in other vertebrate species. This is the first description of the partial JY-1 (exon 3 and 3’UTR) in a livestock species other than cattle and buffalo. The sequence was characterized in a panel of nine Indian goat breeds, which differ in reproductive traits (twinning percentage and age of sexual maturity). Forty three variations were recorded in the analysed region of goats JY-1 compared with cattle. Nucleotide variations in the codifying region of goats correspond to seven amino acid changes that could affect the biological function of the protein and possibly reproductive differences between goats (higher proportion of multiparous animals) and cattle (mainly uniparous). A novel single nucleotide polymorphism (C15329T) has been identified in Indian goats, which was genotyped in 272 animals from six breeds. Further studies to investigate other regions of the gene and its expression in goat female reproductive tissues would clarify the role of JY-1 in farm animal species that are not primarily uniparous.
    Full-text · Article · Aug 2015 · South African Journal Of Animal Science
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    • "Depletion of JY-1 transcripts in zygote stage embryos results in considerably reduced rates of development to the 8–16 cell stage and blastocyst compared to controls. Interestingly, five putative E-box motifs have been identified within 500 bp upstream of the JY-1 transcription start site (TSS) (Bettegowda et al. 2007). Out of the five putative E-box motifs, three have CAGCTG E-box motif and the one E-box adjoining TSS has a CACGTG motif, a well-known USF transcription factor binding sequence. "
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    ABSTRACT: Upstream stimulating factor 1 (USF1) is a basic helix loop helix transcription factor that specifically binds to E-box DNA motifs, known cis-elements of key oocyte expressed genes essential for oocyte and early embryo development. However, the functional and regulatory role of USF1 in bovine oocyte and embryo development is not understood. In this study, we demonstrated that USF1 mRNA is maternal in origin and expressed in a stage specific manner during the course of oocyte maturation and preimplantation embryonic development. Immunocytochemical analysis showed detectable USF1 protein during oocyte maturation and early embryonic development with increased abundance in cytoplasm and nucleus at 8-16 cell stage of embryo development, suggesting a potential role in embryonic genome activation. Knockdown of USF1 in germinal vesicle stage oocytes did not impact meiotic maturation or cumulus expansion, but caused significant changes in mRNA abundance for genes associated with oocyte developmental competence. Furthermore, siRNA mediated depletion of USF1 in presumptive zygote stage embryos demonstrated that USF1 is required for early embryonic development to the blastocyst stage. A similar (USF2) yet unique (TWIST2) expression pattern during oocyte and early embryonic development for related E box binding transcription factors known to cooperatively bind USF1 suggest a potential link to USF1 action. This study demonstrates that USF1 is a maternally derived transcription factor required for bovine early embryonic development which also functions in regulation of JY-1 and GDF9 genes associated with oocyte competence.
    Full-text · Article · Nov 2014 · Reproduction (Cambridge, England)
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    • "Application of functional genomics and siRNA mediated gene knockdown technologies in our laboratory has provide novel insight on intrinsic oocyte derived factors linked to oocyte competence and embryo developmental progression. Our published results established that the JY-1 gene encodes for a species specific secreted protein belonging to a novel protein family with activity of JY-1 required both pre-(Lee et al., unpublished) and postfertilization (Bettegowda et al. 2007) to ensure normal embryo developmental progression. However, the intracellular mechanisms whereby JY-1 promotes early embryogenesis and the relationship between endogenous oocyte JY-1 levels and oocyte competence and fertility in a production setting are not known, but critical to further understanding the role and significance of JY-1 to the reproductive process in cattle. "
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    ABSTRACT: Despite several decades since the birth of the first test tube baby and the first calf derived from an in vitro-fertilised embryo, the efficiency of assisted reproductive technologies remains less than ideal. Poor oocyte competence is a major factor limiting the efficiency of in vitro embryo production. Developmental competence obtained during oocyte growth and maturation establishes the foundation for successful fertilisation and preimplantation embryonic development. Regulation of molecular and cellular events during fertilisation and embryo development is mediated, in part, by oocyte-derived factors acquired during oocyte growth and maturation and programmed by factors of follicular somatic cell origin. The available evidence supports an important intrinsic role for oocyte-derived follistatin and JY-1 proteins in mediating embryo developmental progression after fertilisation, and suggests that the paracrine and autocrine actions of oocyte-derived growth differentiation factor 9, bone morphogenetic protein 15 and follicular somatic cell-derived members of the fibroblast growth factor family impact oocyte competence and subsequent embryo developmental progression after fertilisation. An increased understanding of the molecular mechanisms mediating oocyte competence and stage-specific developmental events during early embryogenesis is crucial for further improvements in assisted reproductive technologies.
    Full-text · Article · Dec 2013 · Reproduction Fertility and Development
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