DLGAP5的缺失通过破坏PI3K-AKT信号轴损害人类和小鼠卵母细胞的成熟
Loss of DLGAP5 impairs human and mouse oocyte maturation via disrupting the PI3K-AKT signaling axis.
摘要(中文译文)
目前，已知的卵母细胞发育异常的遗传原因仅能解释少数女性不孕症。在我们之前的研究中，discs large-associated protein 5（DLGAP5）中的c.1101 C > G，p.Tyr367*突变被鉴定为人类卵母细胞成熟异常和女性不孕症的一种新的遗传原因。本研究旨在验证DLGAP5在卵母细胞成熟中的功能，并进一步探索DLGAP5调控卵母细胞减数分裂的潜在机制。细胞实验阐明，DLGAP5参与细胞分裂，其缺失诱导G2/M期阻滞。通过显微注射siRNAs敲低人类卵母细胞中的DLGAP5，导致纺锤体形态异常和卵母细胞成熟缺陷，表现为生发泡破裂和第一极体排出率降低。此外，在Dlgap5缺陷的小鼠卵母细胞中观察到类似的卵母细胞发育异常表型，而通过显微注射DLGAP5 cRNA可以挽救该表型。进一步，单细胞RNA测序显示，Dlgap5敲除改变了卵母细胞中参与减数分裂过程的基因表达，并使PI3K-AKT信号通路失活。而PI3K-AKT激活剂促进了Dlgap5缺陷小鼠的卵母细胞成熟恢复。DLGAP5已被证明通过激活PI3K-AKT通路调控卵母细胞成熟过程。这强化了DLGAP5功能在卵母细胞成熟调控中的重要作用，并揭示了其潜在机制。它为不孕症患者的临床咨询、遗传诊断和治疗策略提供了关键见解。
Abstract
At present, the known genetic causes of abnormal oocyte development can only account for a minority of female infertility. In our previous study, the mutation c.1101 C > G, p.Tyr367* in discs large-associated protein 5 (DLGAP5) was identified as a novel genetic cause of human oocyte maturation abnormality and female infertility. The present study aimed to validate the function of DLGAP5 in oocyte maturation and further explore the underlying mechanism by which DLGAP5 regulates oocyte meiosis. Cell experiments elucidated that DLGAP5 participates in cell division, and its depletion induced G2/M arrest. The depletion of DLGAP5 in human oocytes by microinjection of siRNAs resulted in abnormal spindle morphology and oocyte maturation defects, exhibiting reduced germinal vesicle breakdown and polar body 1 extrusion rate. In addition, a similar phenotype of abnormal oocyte development was observed in Dlgap5-deficient mouse oocytes, which could be rescued by DLGAP5 cRNA microinjection. Furthermore, single-cell RNA Sequencing showed Dlgap5 knockout altered expression of genes involving in meiosis process in oocytes and deactivated PI3K-AKT signaling pathway. And PI3K-AKT activators facilitated the oocyte maturation resumption in Dlgap5-deficient mice. DLGAP5 has been demonstrated to regulate the process of oocyte maturation via the activation of PI3K-AKT pathway. It reinforces the significant role of DLGAP5 function in oocyte maturation regulation and reveals the underlying mechanism. It provides crucial insights into clinical consultation, genetic diagnosis, and treatment strategies among infertile patients.
如何引用
AMA
Meng Wang, Juepu Zhou, Youzhu Li, Zhou Li, Rui Long, Xiangfei Wang, et al. Loss of DLGAP5 impairs human and mouse oocyte maturation via disrupting the PI3K-AKT signaling axis.. Journal of ovarian research. 2026; doi:10.1186/s13048-026-02134-6.
APA
Meng Wang, Juepu Zhou, Youzhu Li, Zhou Li, Rui Long, Xiangfei Wang, et al (2026). Loss of DLGAP5 impairs human and mouse oocyte maturation via disrupting the PI3K-AKT signaling axis.. Journal of ovarian research. https://doi.org/10.1186/s13048-026-02134-6
GB/T 7714
Meng Wang, Juepu Zhou, Youzhu Li, Zhou Li, Rui Long, Xiangfei Wang, et al. Loss of DLGAP5 impairs human and mouse oocyte maturation via disrupting the PI3K-AKT signaling axis.[J]. Journal of ovarian research, 2026 doi:10.1186/s13048-026-02134-6.
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