دورية أكاديمية
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Identification of zona pellucida defects revealed a novel loss-of-function mutation in ZP2 in humans and rats.

التفاصيل البيبلوغرافية
العنوان: Identification of zona pellucida defects revealed a novel loss-of-function mutation in ZP2 in humans and rats.
المؤلفون: Zeng J; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Sun Y; Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China., Zhang J; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Wu X; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Wang Y; Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China., Quan R; Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China., Song W; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Guo D; Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China., Wang S; Center of Reproductive Health, School of Basic Medical Science, Central South University, Changsha, Hunan, China., Chen J; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Xiao H; Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China.; Center of Reproductive Health, School of Basic Medical Science, Central South University, Changsha, Hunan, China., Huang HL; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
المصدر: Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 May 24; Vol. 14, pp. 1169378. Date of Electronic Publication: 2023 May 24 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Zona Pellucida*/metabolism , Semen*/metabolism, Humans ; Male ; Female ; Rats ; Animals ; Zona Pellucida Glycoproteins/genetics ; Zona Pellucida Glycoproteins/metabolism ; Mutation ; Transforming Growth Factor beta/metabolism
مستخلص: Introduction: Human zona pellucida (ZP) plays an important role in reproductive process. Several rare mutations in the encoding genes ( ZP1 , ZP2 , and ZP3 ) have been demonstrated to cause women infertility. Mutations in ZP2 have been reported to cause ZP defects or empty follicle syndrome. We aimed to identify pathogenic variants in an infertile woman with a thin zona pellucida (ZP) phenotype and investigated the effect of ZP defects on oocyte gene transcription.
Methods: We performed whole-exome sequencing and Sanger sequencing of genes were performed for infertilite patients characterized by fertilization failure in routine in vitro fertilization (IVF). Immunofluorescence (IF) and intracytoplasmic sperm injection (ICSI) were used in the mutant oocytes. Single-cell RNA sequencing was used to investigate transcriptomes of the gene-edited ( Zp2 mut/mut ) rat model. Biological function enrichment analysis, quantitative real-time PCR (qRT-PCR), and IF were performed.
Results: We identified a novel homozygous nonsense mutation of ZP2 (c.1924C > T, p.Arg642X) in a patient with non-consanguineous married parents. All oocytes showed a thin or no ZP under a light microscope and were fertilized after ICSI. The patient successfully conceived by receiving the only two embryos that developed to the blastocyst stage. The immunofluorescence staining showed an apparently abnormal form of the stopped oocytes. We further demonstrated a total of 374 differentially expressed genes (DEGs) in the transcriptome profiles of Zp2 mut/mut rats oocytes and highlighted the signal communication between oocytes and granulosa cells. The pathway enrichment results of DEGs showed that they were enriched in multiple signaling pathways, especially the transforming growth factor-β (TGF-β) signaling pathway in oocyte development. qRT-PCR, IF, and phosphorylation analysis showed significantly downregulated expressions of Acvr2b, Smad2, p38MAPK, and Bcl2 and increased cleaved-caspase 3 protein expression.
Discussion: Our findings expanded the known mutational spectrum of ZP2 associated with thin ZP and natural fertilization failure. Disruption of the integrity of the ZP impaired the TGF-β signaling pathway between oocytes and surrounding granulosa cells, leading to increased apoptosis and decreased developmental potential of oocytes.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Zeng, Sun, Zhang, Wu, Wang, Quan, Song, Guo, Wang, Chen, Xiao and Huang.)
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فهرسة مساهمة: Keywords: TGF-β signaling pathway; ZP2; female infertility; rat model; single-cell RNA sequencing
المشرفين على المادة: 0 (Zona Pellucida Glycoproteins)
0 (Transforming Growth Factor beta)
0 (ZP2 protein, human)
تواريخ الأحداث: Date Created: 20230609 Date Completed: 20230612 Latest Revision: 20240227
رمز التحديث: 20240227
مُعرف محوري في PubMed: PMC10244809
DOI: 10.3389/fendo.2023.1169378
PMID: 37293489
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-2392
DOI:10.3389/fendo.2023.1169378