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

Abstract

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.T he oocyte is a key regulator of multiple aspects of female fertility, including ovarian follicular development and early embryogenesis (1). The advent of oocyte genomics and EST sequencing projects have led to a dramatic increase in our understanding about the identities and functions of oocytespecific genes in female reproduction (2, 3). However, inherent species-specific differences exist in the ovulation quota, follicular waves, duration of the ovarian cycle, and number of embryonic cell cycles required for embryonic genome activation (4) between the traditional animal model (polyovulatory mouse) versus monoovulatory species such as cattle and primates, including humans. Numerous examples suggest that oocytespecific genes identified in the mouse may not have identical functions in other species. For instance, Belclare and Cambridge ewes with naturally occurring heterozygous mutations in the GDF9 gene have an increased ovulation rate and litter size (5), but mice heterozygous for the GDF9 gene disruption exhibit no obvious phenotype (6). Similarly, Inverdale and Hanna strains of sheep with homozygous mutations in BMP15 are infertile (7, 8), whereas homozygous BMP15 mutant mice are subfertile with defects in ovulation and fertilization (9). Thus, comparative genomics approaches coupled to functional studies in nontraditional model systems are needed to address dissimilarities in transcriptome composition between model organisms and provide information on existence of genes or gene families that may play important regulatory roles in fertility in nonmurine models, including the human. With this goal in mind, we previously constructed a bovine oocyte cDNA library and sequenced a number of ESTs (2). A highly abundant transcript (designat...

Identification of some unknown transcripts from SSH cDNA library of buffalo follicular oocytes

“…Over the last decade, vast insight has been gained about molecular events involved in oocyte function in several mammalian species, by identifying genes preferentially expressed in oocytes (Bettegowda et al, 2007;Gaska et al, 2007;Baillet et al, 2008;Parrish et al, 2011). In spite of their economic importance in dairy production, however, buffalo remains a relatively unexplored species particularly in terms of explaining their reproduction disadvantages.…”

“…Continued identification of new oocyte-specific genes and their functional annotation is providing additional insight into the molecular mechanism involved in folliculogenesis, oogenesis, fertilization and early embryogenesis (Bettegowda et al, 2007;Wells et al, 2008;Luo et al, 2010). Several techniques such as differentialdisplay reverse transcription-PCR, microarray hybridization, serial analysis of gene expression and cDNA library construction have been used to reinforce the inventory of oocyte-expressed genes.…”

Efectos de los RNAm maternos sobre la maduración del ovocito y el desarrollo embrionario temprano en mamíferos

“…The expression of the messenger that encodes for KPNA7, is abundant in immature oocytes and oocytes in metaphase II, as well as in embryos in the early stages before the embryonic genome activation, but is barely detectable in morula and blastocyst; in addition, embryos with the inactive gene KPNA7 result in a decrease in the proportion of embryos developed to the stage of blastocyst (145) . Bettegowda et al (146) discovered and characterized the JY-1 gene, whose protein is specific to the oocyte, is responsible for the…”

“…Así mismo, la expresión del gen MATER ha sido detectado en los ovocitos de folículos primarios, disminuyendo fuertemente durante la maduración, así como durante la división embrionaria, encontrándose mínima en regulation of granulosa cells and plays a key role in the regulation of fertility in mammals, which is related to the presence of single nucleotide polymorphisms simple (SNPs) within exon 3 of the gene (147) . The JY-1 mRNA is detectable throughout the folliculogenesis from immature oocytes to the oocyte at metaphase II; after fertilization it is present in early bovine embryos up to the stage of 8 cells (146) . NOBOX is a protein that acts as a transcription factor (148) , whose messenger is preferentially expressed in the bovine ovary.…”

“…La expresión del mensajero que codifica para KPNA7, es abundante en ovocitos inmaduros y en ovocitos en metafase II, así como en embriones en estadios tempranos antes de la activación del genoma embrionario, pero es apenas detectable en mórula y blastocisto; además embriones con el gen KPNA7 inactivo resultan en un decremento en la proporción de embriones desarrollados hasta el estadio de blastocisto (145) . Bettegowda et al (146) descubrieron y caracterizaron el gen JY-1, cuya proteína es específica del ovocito, se encarga de la regulación de las células de la granulosa y tiene una función clave en la regulación de la fertilidad en mamíferos, que se relaciona con la presencia de polimorfismos de nucleótidos simples (SNPs) dentro del exón 3 del gen (147) . El RNAm de JY-1 es detectable a lo largo de la folículogénesis desde ovocitos inmaduros hasta el ovocito en metafase II; después de la fertilización está presente en embriones tempranos de bovino hasta la etapa de 8 células (146) .…”