Article
Genetics & Heredity
Haiyan Guo, Haibo Wu, Zheng Yan, Mingru Yin, Ling Wu, Bin Li
Summary: The occurrence of unexplained fertilization failure can have significant consequences for couples struggling with infertility. Genetic mutations in the WEE2 gene have been identified as a potential cause of unexplained fertilization failure, suggesting the importance of genetic testing in predicting the prognosis for infertile couples.
Article
Genetics & Heredity
Jiamin Jin, Xiaomei Tong, Yin-Li Zhang, Weijie Yang, Yerong Ma, Peipei Ren, Feng Zhou, Songying Zhang
Summary: Three novel compound heterozygous WEE2 variants were identified in patients with pronucleus formation failure, leading to reduced levels of WEE2 protein in oocytes. In vitro experiments showed that mutant WEE2 gene caused decreased WEE2 protein levels or subcellular translocation in HeLa cells, resulting in decreased levels of phosphorylated Cdc2 protein.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2021)
Article
Endocrinology & Metabolism
Ancong Wang, Shan Huang, Min Liu, Baosong Wang, Fengxia Wu, Dongyi Zhu, Xiangyu Zhao
Summary: This study identified novel compound heterozygous mutations of the WEE2 gene in a female with fertilization failure through clinical exome sequencing, expanding the spectrum of WEE2 mutations and enhancing the prognostic value of testing for WEE2 mutations in infertile women with fertilization failure.
GYNECOLOGICAL ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaopei Zhou, Qingsong Xi, Weimin Jia, Zhou Li, Zhenxing Liu, Geng Luo, Chenxi Xing, Dazhi Zhang, Meiqi Hou, Huihui Liu, Xue Yang, Yalin Luo, Xuejie Peng, Guihua Wang, Tingting Zou, Lixia Zhu, Lei Jin, Xianqin Zhang
Summary: Male infertility is a global public health problem with complex pathogenic causes. Through whole-exome sequencing, we identified a novel homozygous missense mutation in the ACTL7A gene in two infertile brothers with teratozoospermia. In vitro fertilization and intracytoplasmic sperm injection showed fertilization failure, and further analysis revealed irregular perinuclear theca (PT) and acrosomal ultrastructural defects in the sperm of these patients. The mutation also caused abnormal localization and reduced expression of PLCZ1, which may contribute to the fertilization failure. This study expands the understanding of ACTL7A mutations and provides a basis for genetic counseling.
MOLECULAR GENETICS AND GENOMICS
(2023)
Article
Cell Biology
Lin Zhao, Yichun Guan, Qingxia Meng, Weijie Wang, Ling Wu, Biaobang Chen, Jijun Hu, Jiawei Zhu, Zhihua Zhang, Jian Mu, Yao Chen, Yiming Sun, Tianyu Wu, Wenjing Wang, Zhou Zhou, Jie Dong, Yang Zeng, Ruyi Liu, Qiaoli Li, Jing Du, Yanping Kuang, Qing Sang, Lei Wang
Summary: Mutations in the CDC20 gene play a crucial role in oocyte maturation and fertilization, leading to various infertility phenotypes. This study expands the spectrum of known mutations in CDC20 and provides new evidence for its involvement in female infertility characterized by oocyte maturation arrest and fertilization failure.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Endocrinology & Metabolism
Yamei Xue, Xiaohong Cheng, Yuping Xiong, Kun Li
Summary: This review summarizes and discusses the mutations of nine important genes associated with fertilization failure in infertile patients. The review highlights their roles in the fertilization process and suggests these mutations as potential targets for precision treatments in reproductive medicine. Furthermore, the review provides helpful clues for genetic counseling and optimizing clinical treatments for human infertility by supplying timely information on the genetic causes of fertilization failure.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Peng Yang, Dongsheng Zhang, Tuo Wang, Jiangzhou Ji, Chi Jin, Chaofan Peng, Yuqian Tan, Jiahui Zhou, Lu Wang, Yifei Feng, Yueming Sun
Summary: In this study, it was found that WEE2-AS1 is highly expressed in CAF-derived sEVs in the tumor microenvironment. The level of WEE2-AS1 is elevated in plasma sEVs of CRC patients, which is associated with advanced pathological staging and poor survival. Functional experiments revealed that elevated expression of WEE2-AS1 in sEVs increases CRC cell proliferation and promotes tumor formation and progression. Mechanistically, WEE2-AS1 interacts with MOB1A, inhibits the Hippo pathway, and facilitates the growth of CRC cells.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Meng Wang, Lixia Zhu, Chang Liu, Hui He, Cheng Wang, Chenxi Xing, Jinming Liu, Liu Yang, Qingsong Xi, Zhou Li, Lei Jin
Summary: The study demonstrates that a new AOA method combining cycloheximide and ionomycin significantly increases fertilization rates for most TFF patients, potentially offering therapeutic benefits for couples experiencing severe fertilization deficiencies even after conventional AOA treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Obstetrics & Gynecology
Gerard Campos, Romualdo Sciorio, Sandro C. Esteves
Summary: Total fertilization failure is the failure of all metaphase II oocytes to fertilize in assisted reproduction cycles. Oocyte activation deficiency is the main cause of fertilization failure, attributed to sperm or oocyte issues. Diagnostic testing and artificial oocyte activation treatments are crucial for overcoming fertilization failure.
HUMAN REPRODUCTION UPDATE
(2023)
Article
Medicine, Research & Experimental
Boyan Li, Rongrong Zhao, Wei Qiu, Ziwen Pan, Shulin Zhao, Yanhua Qi, Jiawei Qiu, Shouji Zhang, Qindong Guo, Yang Fan, Hao Xu, Ming Li, Gang Li, Hao Xue
Summary: This study reveals the differential expression profile of m6A-modified lncRNAs in human GBM tissues for the first time. It identifies WEE2-AS1 as an m6A-modified lncRNA that promotes GBM progression by stabilizing RPN2 protein and activating the PI3K-Akt signaling pathway. Additionally, the study demonstrates that blocking WEE2-AS1 expression improves the therapeutic sensitivity of dasatinib in GBM.
Article
Genetics & Heredity
Fa-Li Zhang, Shu-Er Zhang, Yu-Jiang Sun, Jun-Jie Wang, Wei Shen
Summary: This study used comparative transcriptomic analysis and weighted gene co-expression network analysis (WGCNA) to uncover the uniqueness of donkey oocyte development compared to other animals. It was found that donkey oocytes express a large number of genes related to RNA metabolism and are involved in the negative regulation of cell development.
FRONTIERS IN GENETICS
(2022)
Article
Endocrinology & Metabolism
Mingzhao Li, Miaomiao Jia, Xiaoli Zhao, Rong Shi, Xia Xue
Summary: A new NLRP5 mutation has been identified as causing female infertility and total fertilization failure. This study aims to uncover the genetic reasons for TFF, with only PLCZ1, TLE6, and WEE2 mutations known to result in human fertilization failure.
GYNECOLOGICAL ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Jie Bao, Lixue Chen, Yongxiu Hao, Hongping Wu, Xiaojin He, Chuncheng Lu, Xinhua Ji, Jie Qiao, Yuanyuan Wang, Hongbin Chi
Summary: The study investigated the prevalence and prognosis of congenital anomalies in IVF/ICSI pregnancies, finding that pregnancies with higher fertilization failure rates were more likely to have poor prognoses for fetuses or neonates with congenital anomalies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Xuqiang Zhu, Di Chen, Yiyu Sun, Shuo Yang, Weiguang Wang, Bing Liu, Peng Gao, Xueyuan Li, Lixin Wu, Siqi Ma, Wenyang Lin, Jiwei Ma, Dongming Yan
Summary: This study aimed to assess the value of WEE2-AS1 as a potential prognostic marker of glioma. The findings showed that WEE2-AS1 is overexpressed in various cancers, including glioma, and is associated with glioma progression. It was also determined that WEE2-AS1 expression may serve as an independent risk factor for the survival and prognosis of glioma patients.
Article
Multidisciplinary Sciences
Jessica Joshua, Jeff Caswell, M. Lynne O'Sullivan, Geoffrey Wood, Sonja Fonfara
Summary: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, characterized by left ventricular hypertrophy. It is suggested as a translational animal model for the human disease. This study identified distinct gene expression patterns and pathways associated with HCM in cats, which are related to cardiac remodeling and fibrosis, inflammation, microvascular changes, calcium signaling, and cardiac metabolism.
Article
Genetics & Heredity
Zhihua Zhang, Bin Li, Jing Fu, Rong Li, Feiyang Diao, Caihong Li, Biaobang Chen, Jing Du, Zhou Zhou, Jian Mu, Zheng Yan, Ling Wu, Shuai Liu, Wenjing Wang, Lin Zhao, Jie Dong, Lin He, Xiaozhen Liang, Yanping Kuang, Xiaoxi Sun, Qing Sang, Lei Wang
AMERICAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Genetics & Heredity
Lin Zhao, Yichun Guan, Wenjing Wang, Biaobang Chen, Shiru Xu, Ling Wu, Zheng Yan, Bin Li, Jing Fu, Rong Shi, Juanzi Shi, Jing Du, Qiaoli Li, Zhihua Zhang, Jian Mu, Zhou Zhou, Jie Dong, Li Jin, Lin He, Xiaoxi Sun, Yanping Kuang, Lei Wang, Qing Sang
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2020)
Letter
Cell Biology
Lin Zhao, Songguo Xue, Zhongyuan Yao, Juanzi Shi, Biaobang Chen, Ling Wu, Lihua Sun, Yao Xu, Zheng Yan, Bin Li, Xiaoyan Mao, Jing Fu, Zhihua Zhang, Jian Mu, Wenjing Wang, Jing Du, Shuai Liu, Jie Dong, Weijie Wang, Qiaoli Li, Lin He, Li Jin, Xiaozhen Liang, Yanping Kuang, Xiaoxi Sun, Lei Wang, Qing Sang
Article
Genetics & Heredity
Zhihua Zhang, Ling Wu, Feiyang Diao, Biaobang Chen, Jing Fu, Xiaoyan Mao, Zheng Yan, Bin Li, Jian Mu, Zhou Zhou, Wenjing Wang, Lin Zhao, Jie Dong, Yang Zeng, Jing Du, Yanping Kuang, Xiaoxi Sun, Lin He, Qing Sang, Lei Wang
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2020)
Article
Biochemistry & Molecular Biology
Weijie Wang, Ronggui Qu, Qian Dou, Fengyan Wu, Wenjing Wang, Biaobang Chen, Jian Mu, Zhihua Zhang, Lin Zhao, Zhou Zhou, Jie Dong, Yang Zeng, Ruyi Liu, Jing Du, Shujia Zhu, Qiaoli Li, Lin He, Li Jin, Lei Wang, Qing Sang
Summary: This study identified two novel homozygous missense variants in PANX1 associated with the oocyte death phenotype, expanding the inheritance pattern of PANX1 variants to an autosomal recessive mode. The destructive effect of these homozygous variants on PANX1 function was weaker than that of previously reported heterozygous variants, highlighting the critical role of PANX1 in human oocyte development.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Cell Biology
Lin Zhao, Yichun Guan, Qingxia Meng, Weijie Wang, Ling Wu, Biaobang Chen, Jijun Hu, Jiawei Zhu, Zhihua Zhang, Jian Mu, Yao Chen, Yiming Sun, Tianyu Wu, Wenjing Wang, Zhou Zhou, Jie Dong, Yang Zeng, Ruyi Liu, Qiaoli Li, Jing Du, Yanping Kuang, Qing Sang, Lei Wang
Summary: Mutations in the CDC20 gene play a crucial role in oocyte maturation and fertilization, leading to various infertility phenotypes. This study expands the spectrum of known mutations in CDC20 and provides new evidence for its involvement in female infertility characterized by oocyte maturation arrest and fertilization failure.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Obstetrics & Gynecology
Jie Dong, Hong Zhang, Xiaoyan Mao, Junhua Zhu, Da Li, Jing Fu, Jijun Hu, Ling Wu, Biaobang Chen, Yiming Sun, Jian Mu, Zhihua Zhang, Xiaoxi Sun, Lin Zhao, Wenjing Wang, Weijie Wang, Zhou Zhou, Yang Zeng, Jing Du, Qiaoli Li, Lin He, Li Jin, Yanping Kuang, Lei Wang, Qing Sang
Summary: Novel mutations in MEI1 were found to cause new phenotypes such as early embryonic arrest and recurrent implantation failure. This expands the understanding of the role of MEI1 in human oocyte meiosis and early embryonic development.
HUMAN REPRODUCTION
(2021)
Article
Obstetrics & Gynecology
Weijie Wang, Wenjing Wang, Yao Xu, Juanzi Shi, Jing Fu, Biaobang Chen, Jian Mu, Zhihua Zhang, Lin Zhao, Jing Lin, Jing Du, Qiaoli Li, Lin He, Li Jin, Xiaoxi Sun, Lei Wang, Qing Sang
Summary: This study identified three pathogenic variants in FBXO43 that are associated with early embryonic arrest in humans. By investigating the effects of these variants in cells and mouse oocytes, a causal relationship between FBXO43 and female infertility was established. These findings contribute to understanding the role of FBXO43 in human early embryonic development and provide a new genetic marker for female infertility.
HUMAN REPRODUCTION
(2021)
Article
Obstetrics & Gynecology
Ruyi Liu, Zheng Yan, Yong Fan, Ronggui Qu, Biaobang Chen, Bin Li, Ling Wu, Haibo Wu, Jian Mu, Lin Zhao, Wenjing Wang, Jie Dong, Yang Zeng, Qiaoli Li, Lei Wang, Qing Sang, Zhihua Zhang, Yanping Kuang
Summary: Our study identified bi-allelic variants in KCNU1 as novel pathogenetic genes for male infertility, particularly due to impaired sperm acrosome reactions. These findings were confirmed through functional studies and treatment strategies using a knock-in mouse model, where deficiencies were rescued through intracytoplasmic sperm injection.
HUMAN REPRODUCTION
(2022)
Article
Genetics & Heredity
Lin Zhao, Qun Li, Yanping Kuang, Peng Xu, Xiaoxi Sun, Qingxia Meng, Wenjing Wang, Yang Zeng, Biaobang Chen, Jing Fu, Jie Dong, Jiawei Zhu, Yuxi Luo, Hao Gu, Caihong Li, Chunyi Li, Ling Wu, Xiaoyan Mao, Huizhen Fan, Ruyi Liu, Zhihua Zhang, Qiaoli Li, Jing Du, Lin He, Li Jin, Lei Wang, Qing Sang
Summary: This study identified a novel pathogenic gene LHX8 through a gene-based burden test and established the causative relationship between LHX8 haploinsufficiency and female infertility characterized by oocyte maturation arrest.
GENETICS IN MEDICINE
(2022)
Article
Oncology
Weiqiang Zhu, Yan Gu, Min Li, Zhaofeng Zhang, Junwei Liu, Yanyan Mao, Qianxi Zhu, Lin Zhao, Yupei Shen, Fujia Chen, Lingjin Xia, Lin He, Jing Du
Summary: This study investigated the mechanism of recurrent spontaneous abortion (RSA) and its relationship with air pollution exposure. By comparing decidual tissue data from individuals with induced abortions and those with RSA, the study revealed a comprehensive cellular and molecular mechanism of RSA and suggested that air pollution might cause pregnancy loss by affecting the methylation level of the IGF2BP1 promoter.
CLINICAL EPIGENETICS
(2022)
Article
Genetics & Heredity
Ronggui Qu, Zhihua Zhang, Ling Wu, Qun Li, Jian Mu, Lin Zhao, Zheng Yan, Wenjing Wang, Yang Zeng, Ruyi Liu, Jie Dong, Qiaoli Li, Xiaoxi Sun, Lei Wang, Qing Sang, Biaobang Chen, Yanping Kuang
Summary: Variants in the androglobin (ADGB) gene were found to be associated with asthenozoospermia, leading to reduced sperm motility and concentration. The study also identified 42 candidate proteins involved in sperm assembly and motility, with CFAP69 and SPEF2 confirmed to interact with ADGB. These findings highlight the important role of ADGB in human fertility and provide a theoretical basis for using it as a genetic marker for infertile males.
Article
Multidisciplinary Sciences
Lin Zhao, Sabrina R. T. Koseki, Rachel A. Silverstein, Nadia Amrani, Christina Peng, Christian Kramme, Natasha Savic, Martin Pacesa, Tomas C. Rodriguez, Teodora Stan, Emma Tysinger, Lauren Hong, Vivian Yudistyra, Manvitha R. Ponnapati, Joseph M. Jacobson, George M. Church, Noah Jakimo, Ray Truant, Martin Jinek, Benjamin P. Kleinstiver, Erik J. Sontheimer, Pranam Chatterjee
Summary: In this study, a chimeric enzyme SpRYc with highly flexible PAM preference was generated by combining the PAM-interacting domain of SpRY and the N-terminus of Sc++, leveraging properties of both enzymes. SpRYc showed the ability to specifically edit diverse PAMs and disease-related loci, highlighting the power of integrative protein design for Cas9 engineering.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Wenjing Wang, Yoichi Miyamoto, Biaobang Chen, Juanzi Shi, Feiyang Diao, Wei Zheng, Qun Li, Lan Yu, Lin Li, Yao Xu, Ling Wu, Xiaoyan Mao, Jing Fu, Bin Li, Zheng Yan, Rong Shi, Xia Xue, Jian Mu, Zhihua Zhang, Tianyu Wu, Lin Zhao, Weijie Wang, Zhou Zhou, Jie Dong, Qiaoli Li, Li Jin, Lin He, Xiaoxi Sun, Ge Lin, Yanping Kuang, Lei Wang, Qing Sang
Summary: By analyzing whole-exome sequencing data of 606 women with PREMBA, researchers have identified a candidate gene KPNA7, which may contribute to the development of PREMBA. The study further revealed that KPNA7 mutations reduce protein levels, impair its binding capacity to substrate RSL1D1, and affect nuclear transport activity. Furthermore, the study found that mouse KPNA2 plays a critical role in embryonic development and its deficiency leads to embryo arrest, similar to human PREMBA cases. These findings provide a mechanistic understanding of PREMBA and a diagnostic marker for PREMBA patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biotechnology & Applied Microbiology
Qun Li, Lin Zhao, Yang Zeng, Yanping Kuang, Yichun Guan, Biaobang Chen, Shiru Xu, Bin Tang, Ling Wu, Xiaoyan Mao, Xiaoxi Sun, Juanzi Shi, Peng Xu, Feiyang Diao, Songguo Xue, Shihua Bao, Qingxia Meng, Ping Yuan, Wenjun Wang, Ning Ma, Di Song, Bei Xu, Jie Dong, Jian Mu, Zhihua Zhang, Huizhen Fan, Hao Gu, Qiaoli Li, Lin He, Li Jin, Lei Wang, Qing Sang
Summary: In this study, we investigated the role of de novo mutations (DNMs) in female infertility with oocyte and embryo defects. By analyzing the genetic mutations in 473 infertile parent-child trios, we identified 481 confident DNMs in 474 genes. These genes are enriched in signaling pathways related to female reproductive processes. Further functional assays showed that mutations in the TUBA4A gene disrupt normal cell and mouse reproductive development. These findings provide novel genetic insights into female infertility and offer potential genetic markers for the diagnosis of assisted reproductive technology failure.