NCBI Summary:
The protein encoded by this gene belongs to the KHDC1 family, members of which contain an atypical KH domain that may not bind RNA like canonical KH domains. This gene is specifically expressed in the oocytes, and recent studies suggest that it may function as a regulator of genomic imprinting in the oocyte. Mutations in this gene are associated with recurrent biparental complete hydatidiform mole. [provided by RefSeq, Dec 2011]
General function
, Epigenetic modifications
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Cellular localization
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Ovarian function
Oocyte maturation, Early embryo development
Comment
ECAT1 is essential for human oocyte maturation and pre-implantation development of the resulting embryos. Liu C et al. (2016) ECAT1 is a subunit of the subcortical maternal complex that is required for cell cycle progression during pre-implantation embryonic development; however, its exact function remains to be elucidated. Here we investigated the expression of ECAT1 in human ovarian tissue, oocytes and pre-implantation embryos and assessed its function by using RNA interference (RNAi) in oocytes. ECAT1 mRNA was highly expressed in human oocytes and zygotes, as well as in two-cell, four-cell and eight-cell embryos, but declined significantly in morulae and blastocysts. ECAT1 was expressed in the cytoplasm of oocytes and pre-implantation embryos and was localized more specifically in the cortical region than in the inner cytoplasm. RNAi experiments demonstrated that down-regulation of ECAT1 expression not only impaired spindle assembly and reduced maturation and fertilization rates of human oocytes but also decreased the cleavage rate of the resulting zygotes. In conclusion, our study indicates that ECAT1 may play a role in meiotic progression by maintaining the accuracy of spindle assembly in human oocytes, thus promoting oocyte maturation and subsequent development of the embryo.//////////////////
Expression of Bovine Ecat1 Gene in Immature and in vitro Matured Oocytes as Well as During Early Embryonic Development. Zahmatkesh A et al. (2015) Ecat1 is a maternal effect gene that is exclusively expressed in oocytes and embryonic stem cells, and has an important role in pre-implantation development. This study was designed to investigate the expression of bovine Ecat1 gene in immature and in vitro matured oocytes as well as during early embryonic development, and also Ecat1 protein localization. Samples were obtained from slaughtered animals. RNA extractions were carried out from ovary, immature and in vitro matured oocytes and also different stages of embryonic development (2-, 4-, 8- to 16-cell stages and blastocysts). RT-PCR analysis revealed the expression of Ecat1 in ovary, oocytes and embryos. Analysis in FGENESH online tool predicted three exons and one transcription start site (TSS) in Ecat1 gene, and the 3' RACE-PCR result showed that just one splice variant was amplified. By quantitative real-time PCR technique, we showed that Ecat1 transcript increased at 8- to 16-cell-stage embryos and decreased in blastocyst stage (p < 0.05). Immunofluorescence analysis showed cytoplasmic localization of Ecat1 protein in bovine oocytes. Results demonstrated bovine Ecat1 expression at protein level and also indicated that Ecat1 has a significant higher embryonic expression at 8- to 16-cell stage. This embryonic expression is probably required for further developmental stages.//////////////////
Expression regulated by
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Ovarian localization
Oocyte
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Identification of maturation-specific proteins by single-cell proteomics of human oocytes. Virant-Klun I et al. (2016) Oocytes undergo a range of complex processes via oogenesis, maturation, fertilization, and early embryonic development, eventually giving rise to a fully functioning organism. To understand proteome composition and diversity during maturation of human oocytes, here we have addressed crucial aspects of oocyte collection and proteome analysis resulting in the first proteome and secretome maps of human oocytes. Starting from 100 oocytes collected via a novel serum-free hanging drop culture system we identified 2,154 proteins, whose function indicate that oocytes are largely resting cells with a proteome that is tailored for homeostasis, cellular attachment and interaction with its environment via secretory factors. In addition, we have identified 158 oocyte-enriched proteins (such as ECAT1, PIWIL3, NLRP7) not observed in high coverage proteomics studies of other human cell lines or tissues. Exploiting SP3, a novel technology for proteomic sample preparation using magnetic beads, we scaled down proteome analysis to single cells. Despite the low protein content of only ~100ng per cell, we consistently identified ~450 proteins from individual oocytes. When comparing individual oocytes at the germinal vesicle (GV) and metaphase II (MII) stage we found that the Tudor and KH domain-containing protein (TDRKH) is preferentially expressed in immature oocytes, while Wee2, PCNA and DNMT1 were enriched in mature cells, collectively indicating that maintenance of genome integrity is crucial during oocyte maturation. This study demonstrates that an innovative proteomics workflow facilitates analysis of single human oocytes, to investigate human oocyte biology and pre-implantation development. The approach presented here paves the way for quantitative proteomics in other quantity-limited tissues and cell types. Data associated with this study are available via ProteomeXchange with identifier PXD003691.//////////////////
Follicle stages
Comment
Phenotypes
Mutations
3 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: infertile - ovarian defect Comment: Mutations Causing Familial Biparental Hydatidiform Mole Implicate C6orf221 as a Possible Regulator of Genomic Imprinting in the Human Oocyte. Parry DA et al. Familial biparental hydatidiform mole (FBHM) is the only known pure maternal-effect recessive inherited disorder in humans. Affected women, although developmentally normal themselves, suffer repeated pregnancy loss because of the development of the conceptus into a complete hydatidiform mole in which extraembryonic trophoblastic tissue develops but the embryo itself suffers early demise. This developmental phenotype results from a genome-wide failure to correctly specify or maintain a maternal epigenotype at imprinted loci. Most cases of FBHM result from mutations of NLRP7, but genetic heterogeneity has been demonstrated. Here, we report biallelic mutations of C6orf221 in three families with FBHM. The previously described biological properties of their respective gene families suggest that NLRP7 and C6orf221 may interact as components of an oocyte complex that is directly or indirectly required for determination of epigenetic status on the oocyte genome.
Species: mouse
Mutation name: type: null mutation fertility: infertile - ovarian defect Comment: A subcortical maternal complex essential for preimplantation mouse embryogenesis. Li L et al. (2008) We have identified a subcortical maternal complex (SCMC) that assembles during oocyte growth and is essential for zygotes to progress beyond the first embryonic cell divisions. At least four maternally encoded proteins contribute to this MDa complex: FLOPED, MATER, and TLE6 interact with each other while Filia binds independently to MATER. Although the transcripts encoding these proteins are degraded during meiotic maturation and ovulation, the SCMC proteins persist in the early embryo. The SCMC, located in the subcortex of eggs, is excluded from regions of cell-cell contact in the cleavage-stage embryo and segregates to the outer cells of the morulae and blastocyst. Floped(tm/tm) and/or Mater(tm/tm) eggs lack the SCMC but can be fertilized. However, these embryos do not progress beyond cleavage stage development and female mice are sterile. The proteins are conserved in humans, and similar maternal effect mutations may result in recurrent embryonic loss.//////////////////
Species: human
Mutation name: type: naturally occurring fertility: infertile - ovarian defect Comment: Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest. Wang X et al. (2018) Successful human reproduction initiates from normal gamete formation, fertilization and early embryonic development. Abnormalities in any of these steps will lead to infertility. Many infertile patients undergo several failures of IVF and intracytoplasmic sperm injection (ICSI) cycles, and embryonic developmental arrest is a common phenotype in cases of recurrent failure of IVF/ICSI attempts. However, the genetic basis for this phenotype is poorly understood. The subcortical maternal complex (SCMC) genes play important roles during embryonic development, and using whole-exome sequencing novel biallelic mutations in the SCMC genes TLE6, PADI6 and KHDC3L were identified in four patients with embryonic developmental arrest. A mutation in TLE6 was found in a patient with cleaved embryos that arrested on day 3 and failed to form blastocysts. Two patients with embryos that arrested at the cleavage stage had mutations in PADI6, and a mutation in KHDC3L was found in a patient with embryos arrested at the morula stage. No mutations were identified in these genes in an additional 80 patients. These findings provide further evidence for the important roles of TLE6, PADI6 and KHDC3L in embryonic development. This work lays the foundation for the genetic diagnosis of patients with recurrent IVF/ICSI failure.//////////////////