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NLRP14 deficiency causes female infertility with oocyte maturation defects and early embryonic arrest by impairing cytoplasmic UHRF1 abundance.
- Source :
- Cell Reports; Dec2023, Vol. 42 Issue 12, pN.PAG-N.PAG, 1p
- Publication Year :
- 2023
-
Abstract
- Oocyte maturation is vital to attain full competence required for fertilization and embryogenesis. NLRP14 is preferentially expressed in mammalian oocytes and early embryos. Yet, the role and molecular mechanism of NLRP14 in oocyte maturation and early embryogenesis are poorly understood, and whether NLRP14 deficiency accounts for human infertility is unknown. Here, we found that maternal loss of Nlrp14 resulted in sterility with oocyte maturation defects and early embryonic arrest (EEA). Nlrp14 ablation compromised oocyte competence due to impaired cytoplasmic and nuclear maturation. Importantly, we revealed that NLRP14 maintained cytoplasmic UHRF1 abundance by protecting it from proteasome-dependent degradation and anchoring it from nuclear translocation in the oocyte. Furthermore, we identified compound heterozygous NLRP14 variants in women affected by infertility with EEA, which interrupted the NLRP14-UHRF1 interaction and decreased UHRF1 levels. Our data demonstrate NLRP14 as a cytoplasm-specific regulator of UHRF1 during oocyte maturation, providing insights into genetic diagnosis for female infertility. [Display omitted] • NLRP14 is required for oocyte maturation and early embryonic development • Loss of Nlrp14 compromises oocyte competence by impairing nuclear and cytoplasmic maturation • NLRP14 interacts with UHRF1 to regulate its cytoplasmic abundance and localization • NLRP14 variants are identified in women affected by infertility with early embryonic arrest Zhang et al. show that NLRP14 is essential for oocyte maturation and competence required for early embryogenesis. NLRP14 maintains cytoplasmic UHRF1 abundance by protecting it from degradation and anchoring it from nuclear accumulation, and its deficiency accounts for female infertility in both mice and human. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 26391856
- Volume :
- 42
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- 174412344
- Full Text :
- https://doi.org/10.1016/j.celrep.2023.113531