Core fucosylation regulates the ovarian response via FSH receptor during follicular development.

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  • Additional Information
    • Source:
      Publisher: Cairo University, production and hosting by Elsevier B. V Country of Publication: Egypt NLM ID: 101546952 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2090-1224 (Electronic) Linking ISSN: 20901224 NLM ISO Abbreviation: J Adv Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Giza, Egypt] : Cairo University, production and hosting by Elsevier B. V.
    • Subject Terms:
      Receptors, FSH*/metabolism ; Receptors, FSH*/genetics ; Fucosyltransferases*/metabolism ; Fucosyltransferases*/genetics ; Mice, Knockout* ; Granulosa Cells*/metabolism ; Fucose*/metabolism ; Follicle Stimulating Hormone*/metabolism; Animals ; Female ; Mice ; Humans ; Glycosylation ; Oocytes/metabolism ; Ovarian Follicle/metabolism ; Ovary/metabolism ; Adult ; Signal Transduction ; Fertilization in Vitro/methods ; Infertility, Female/metabolism
    • Abstract:
      Introduction: Ovarian low response to follicle-stimulating hormone (FSH) causes infertility featuring hypergonadotropic hypogonadism, ovarian failure, and/or defective ovarian response.
      Objectives: N-glycosylation is essential for FSH receptor (FSHR). Core fucosylation catalyzed by fucosyltransferase 8 (FUT8) is the most common N-glycosylation. Core fucosylation level changes between individuals and plays important roles in multiple physiological and pathological conditions. This study aims to elucidate the significance of FUT8 to modulate FSHR function in female fertility.
      Methods: Samples from patients classified as poor ovary responders (PORs) were detected with lectin blot and real-time PCR. Fut8 gene knockout (Fut8 -/- ) mice and FUT8-knockdown human granulosa cell line (KGN-KD) were established and in vitro fertilization (IVF) assay, western blot, molecular interaction, immunofluorescence and immunoprecipitation were applied.
      Results: Core fucosylation is indispensable for oocyte and follicular development. FSHR is a highly core-fucosylated glycoprotein. Loss of core fucosylation suppressed binding of FSHR to FSH, and attenuated FSHR downstream signaling in granulosa cells. Transcriptomic analysis revealed the downregulation of several transcripts crucial for oocyte meiotic progression and preimplantation development in Fut8 -/- mice and in POR patients. Furthermore, loss of FUT8 inhibited the interaction between granulosa cells and oocytes, reduced transzonal projection (TZP) formation and caused poor developmental competence of oocytes after fertilization in vitro. While L-fucose administration increased the core fucosylation of FSHR, and its sensitivity to FSH.
      Conclusion: This study first reveals a significant presence of core fucosylation in female fertility control. Decreased fucosylation on FSHR reduces the interaction of FSH-FSHR and subsequent signaling, which is a feature of the POR patients. Our results suggest that core fucosylation controls oocyte and follicular development via the FSH/FSHR pathway and is essential for female fertility in mammals.
      (Copyright © 2024. Published by Elsevier B.V.)
    • Contributed Indexing:
      Keywords: Core Fucosylation; Female fertility; Follicle-stimulating hormone receptor (FSHR); Fucosyltransferase 8 (FUT8); Ovarian response
    • Accession Number:
      0 (Receptors, FSH)
      EC 2.4.1.- (Fucosyltransferases)
      28RYY2IV3F (Fucose)
      9002-68-0 (Follicle Stimulating Hormone)
      EC 2.4.1.68 (Glycoprotein 6-alpha-L-fucosyltransferase)
      0 (FSHR protein, human)
    • Publication Date:
      Date Created: 20240127 Date Completed: 20241218 Latest Revision: 20241218
    • Publication Date:
      20241219
    • Accession Number:
      10.1016/j.jare.2024.01.025
    • Accession Number:
      38280716