Dataset Information

X-Linked Huwe1 Is Essential for Oocyte Maturation and Preimplantation Embryo Development.

ABSTRACT: HUWE1 is a HECT-domain ubiquitin E3 ligase expressed in various tissues. Although HUWE1 is known to promote degradation of the tumor suppressor p53, given a growing list of its substrates, in vivo functions of HUWE1 remain elusive. Here, we investigated the role of HUWE1 in the female reproductive system. Homozygous deletion of Huwe1 in mouse oocytes of primary follicles caused oocyte death and female infertility, whereas acute depletion of HUWE1 protein by Trim-Away technology did not impact oocytes from antral follicles. Interestingly, oocytes from Huwe1 heterozygous females matured and fertilized normally, but the majority of embryos that lacked maternal Huwe1 were arrested at the morula stage after fertilization. Consequently, Huwe1 heterozygous females only produced wild-type pups. Concomitant knockout of p53 did not recover fertility of the Huwe1 knockout females. These findings make HUWE1 a unique and critical maternal factor indispensable for maintaining the quality of oocytes and embryos.

SUBMITTER: Eisa AA

PROVIDER: S-EPMC7495106 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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X-Linked Huwe1 Is Essential for Oocyte Maturation and Preimplantation Embryo Development.

Eisa Alaa A AA Bang Scott S Crawford Katherine J KJ Murphy Emily M EM Feng William W WW Dey Souvik S Wells Wendy W Kon Ning N Gu Wei W Mehlmann Lisa M LM Vijayaraghavan Srinivasan S Kurokawa Manabu M

iScience 20200902 9

HUWE1 is a HECT-domain ubiquitin E3 ligase expressed in various tissues. Although HUWE1 is known to promote degradation of the tumor suppressor p53, given a growing list of its substrates, in vivo functions of HUWE1 remain elusive. Here, we investigated the role of HUWE1 in the female reproductive system. Homozygous deletion of Huwe1 in mouse oocytes of primary follicles caused oocyte death and female infertility, whereas acute depletion of HUWE1 protein by Trim-Away technology did ...[more]

PMID: 32927266

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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

X-Linked Huwe1 Is Essential for Oocyte Maturation and Preimplantation Embryo Development.

Publications

X-Linked <i>Huwe1</i> Is Essential for Oocyte Maturation and Preimplantation Embryo Development.

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