Dataset Information

Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development.

ABSTRACT: CTCF is a multifunctional nuclear factor involved in epigenetic regulation. Despite recent advances that include the systematic discovery of CTCF-binding sites throughout the mammalian genome, the in vivo roles of CTCF in adult tissues and during embryonic development are largely unknown. Using transgenic RNAi, we depleted maternal stores of CTCF from growing mouse oocytes, and identified hundreds of misregulated genes. Moreover, our analysis suggests that CTCF predominantly activates or derepresses transcription in oocytes. CTCF depletion causes meiotic defects in the egg, and mitotic defects in the embryo that are accompanied by defects in zygotic gene expression, and culminate in apoptosis. Maternal pronuclear transfer and CTCF mRNA microinjection experiments indicate that CTCF is a mammalian maternal effect gene, and that persistent transcriptional defects rather than persistent chromosomal defects perturb early embryonic development. This is the first study detailing a global and essential role for CTCF in mouse oocytes and preimplantation embryos.

SUBMITTER: Wan LB

PROVIDER: S-EPMC2596970 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development.

Wan Le-Ben LB Pan Hua H Hannenhalli Sridhar S Cheng Yong Y Ma Jun J Fedoriw Andrew A Lobanenkov Victor V Latham Keith E KE Schultz Richard M RM Bartolomei Marisa S MS

Development (Cambridge, England) 20080709 16

CTCF is a multifunctional nuclear factor involved in epigenetic regulation. Despite recent advances that include the systematic discovery of CTCF-binding sites throughout the mammalian genome, the in vivo roles of CTCF in adult tissues and during embryonic development are largely unknown. Using transgenic RNAi, we depleted maternal stores of CTCF from growing mouse oocytes, and identified hundreds of misregulated genes. Moreover, our analysis suggests that CTCF predominantly activates or derepre ...[more]

PMID: 18614575

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Project description:PurposeTo investigate the association between oocyte area and fertilization rate, embryo usage, and preimplantation embryo development in order to establish if oocyte area can be a marker for optimal early embryo development.MethodsFrom 2017 to 2020, 378 couples with an indication for IVF (n = 124) or ICSI (n = 254) were included preconceptionally in the Rotterdam Periconception Cohort. Resulting oocytes (n = 2810) were fertilized and submitted to time-lapse embryo culture. Oocyte area was measured at the moment of fertilization (t0), pronuclear appearance (tPNa), and fading (tPNf). Fertilization rate, embryo usage and quality, and embryo morphokinetics from 2-cell stage to expanded blastocyst stage (t2-tEB) were used as outcome measures in association with oocyte area. Oocytes were termed "used" if they were fertilized and embryo development resulted in transfer or cryopreservation, and otherwise termed "discarded". Analyses were adjusted for relevant confounders.ResultsOocyte area decreased from t0 to tPNf after IVF and ICSI, and oocytes with larger area shrank faster (β - 12.6 µm2/h, 95%CI - 14.6; - 10.5, p < 0.001). Oocytes that resulted in a used embryo were larger at all time-points and reached tPNf faster than oocytes that fertilized but were discarded (oocyte area at tPNf in used 9864 ± 595 µm2 versus discarded 9679 ± 673 µm2, p < 0.001, tPNf in used 23.6 ± 3.2 h versus discarded 25.6 ± 5.9 h, p < 0.001). Larger oocytes had higher odds of being used (oocyte area at tPNf ORused 1.669, 95%CI 1.336; 2.085, p < 0.001), were associated with faster embryo development up to the morula stage (e.g., t9 β - 0.131 min, 95%CI - 0.237; - 0.025, p = 0.016) and higher ICM quality.ConclusionOocyte area is an informative marker for the preimplantation development of the embryo, as a larger oocyte area is associated with higher quality, faster developing embryos, and higher chance of being used. Identifying determinants associated with oocyte and embryo viability and quality could contribute to improved preconception care and subsequently healthy pregnancies.

Dataset Information

Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development.

Publications

Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development.

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