Regulation of bone morphogenetic protein receptor type II expression by FMR1/Fragile X mental retardation protein in human granulosa cells in the context of poor ovarian response

Fragile X mental retardation protein (FMRP) is a translational repressor encoded by FMR1. It targets bone morphogenetic protein receptor type II (BMPR2), which regulates granulosa cell (GC) function and follicle development. However, whether this interaction affects folliculogenesis remains unclear....

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Hauptverfasser: Nguyen, Xuan Phuoc (VerfasserIn) , Vilkaite, Adriana (VerfasserIn) , Bender, Ulrike (VerfasserIn) , Dietrich, Jens Erik (VerfasserIn) , Hinderhofer, Katrin (VerfasserIn) , Strowitzki, Thomas (VerfasserIn) , Rehnitz, Julia (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 3 October 2024
In: International journal of molecular sciences
Year: 2024, Jahrgang: 25, Heft: 19, Pages: 1-14
ISSN:1422-0067
DOI:10.3390/ijms251910643
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms251910643
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/25/19/10643
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Verfasserangaben:Xuan Phuoc Nguyen, Adriana Vilkaite, Ulrike Bender, Jens E. Dietrich, Katrin Hinderhofer, Thomas Strowitzki and Julia Rehnitz

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520 |a Fragile X mental retardation protein (FMRP) is a translational repressor encoded by FMR1. It targets bone morphogenetic protein receptor type II (BMPR2), which regulates granulosa cell (GC) function and follicle development. However, whether this interaction affects folliculogenesis remains unclear. Therefore, this study investigated the potential effect of FMRP-BMPR2 dysregulation in ovarian reserves and infertility. COV434 cells and patient-derived GCs were used to evaluate FMRP and BMPR2 expression. Similarly, FMR1, BMPR2, LIMK1, and SMAD expression were evaluated in GCs with normal (NOR) and poor (POR) ovarian responses. FMRP and BMPR2 were expressed in both cell types. They were co-localized to the nuclear membrane of COV434 cells and cytoplasm of primary GCs. FMR1 silencing increased the mRNA and protein levels of BMPR2. However, the mRNA levels of FMR1 and BMPR2 were significantly lower in the POR group. FMR1 and BMPR2 levels were strongly positively correlated in the NOR group but weakly correlated in the POR group. Additionally, SMAD9 expression was significantly reduced in the POR group. This study highlights the crucial role of FMR1/FMRP in the regulation of BMPR2 expression and its impact on ovarian function. These findings indicate that the disruption of FMRP-BMPR2 interactions may cause poor ovarian responses and infertility. 
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