Cell Reports (Dec 2023)
NLRP14 deficiency causes female infertility with oocyte maturation defects and early embryonic arrest by impairing cytoplasmic UHRF1 abundance
- Wenzhe Zhang,
- Rongrong Zhang,
- Ling Wu,
- Chendi Zhu,
- Chuanxin Zhang,
- Chengpeng Xu,
- Shidou Zhao,
- Xinchen Liu,
- Ting Guo,
- Yueshuang Lu,
- Zheng Gao,
- Xiao Yu,
- Lei Li,
- Zi-Jiang Chen,
- Yingying Qin,
- Xue Jiao
Affiliations
- Wenzhe Zhang
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Rongrong Zhang
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Ling Wu
- The Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
- Chendi Zhu
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Chuanxin Zhang
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Chengpeng Xu
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Stem Cell and Regeneration, Beijing Institute of Stem Cell and Regenerative Medicine, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- Shidou Zhao
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Xinchen Liu
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Ting Guo
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Yueshuang Lu
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Zheng Gao
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, China
- Xiao Yu
- Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China
- Lei Li
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Stem Cell and Regeneration, Beijing Institute of Stem Cell and Regenerative Medicine, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- Zi-Jiang Chen
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China
- Yingying Qin
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China; Corresponding author
- Xue Jiao
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250012, China; Suzhou Research Institute, Shandong University, Suzhou, Jiangsu 215123, China; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 12
p. 113531
Abstract
Summary: 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.
