Department of Gynecological Endocrinology and Fertility Disorders, University Women's Hospital, 69120 Heidelberg, Germany.
Institute of Human Genetics, University Heidelberg, 69120 Heidelberg, Germany.
Int J Mol Sci. 2024 Oct 3;25(19):10643. doi: 10.3390/ijms251910643.
Fragile X mental retardation protein (FMRP) is a translational repressor encoded by . 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, , , , and 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. silencing increased the mRNA and protein levels of BMPR2. However, the mRNA levels of and were significantly lower in the POR group. and levels were strongly positively correlated in the NOR group but weakly correlated in the POR group. Additionally, expression was significantly reduced in the POR group. This study highlights the crucial role of /FMRP in the regulation of expression and its impact on ovarian function. These findings indicate that the disruption of FMRP-BMPR2 interactions may cause poor ovarian responses and infertility.
脆性 X 智力低下蛋白 (FMRP) 是由 编码的翻译抑制剂。它靶向骨形态发生蛋白受体 II 型 (BMPR2)，后者调节颗粒细胞 (GC) 功能和卵泡发育。然而，这种相互作用是否影响卵泡发生尚不清楚。因此，本研究探讨了 FMRP-BMPR2 失调对卵巢储备和不孕的潜在影响。使用 COV434 细胞和患者来源的 GC 来评估 FMRP 和 BMPR2 的表达。同样，在具有正常 (NOR) 和较差 (POR) 卵巢反应的 GC 中评估 、 、 和 的表达。FMRP 和 BMPR2 在两种细胞类型中均有表达。它们在 COV434 细胞的核膜和原代 GC 的细胞质中均有共定位。 沉默增加了 BMPR2 的 mRNA 和蛋白水平。然而，POR 组中 和 的 mRNA 水平明显降低。NOR 组中 和 的水平呈强烈正相关，但 POR 组中呈弱相关。此外，POR 组中 的表达明显降低。本研究强调了 /FMRP 在调节 表达及其对卵巢功能的影响中的关键作用。这些发现表明，FMRP-BMPR2 相互作用的破坏可能导致卵巢反应不良和不孕。
