生物
卵母细胞
MAPK/ERK通路
细胞生物学
激酶
胚胎干细胞
卵母细胞激活
磷酸化
遗传学
分子生物学
基因
胚胎
作者
Yinli Zhang,Wei Zheng,Pengfei Ren,Huiling Hu,Xiaomei Tong,Shuo-Ping Zhang,Xiang Li,Haichao Wang,Jun-Chao Jiang,Jiamin Jin,Weijie Yang,Lan-Rui Cao,Yuanlin He,Yerong Ma,Yingyi Zhang,Yifan Gu,Liang Hu,Keli Luo,Fei Gong,Guangxiu Lu,Ge Lin,Heng-Yu Fan,Songying Zhang
标识
DOI:10.15252/emmm.202114887
摘要
Early embryonic arrest and fragmentation (EEAF) is a common phenomenon leading to female infertility, but the genetic determinants remain largely unknown. The Moloney sarcoma oncogene (MOS) encodes a serine/threonine kinase that activates the ERK signaling cascade during oocyte maturation in vertebrates. Here, we identified four rare variants of MOS in three infertile female individuals with EEAF that followed a recessive inheritance pattern. These MOS variants encoded proteins that resulted in decreased phosphorylated ERK1/2 level in cells and oocytes, and displayed attenuated rescuing effects on cortical F-actin assembly. Using oocyte-specific Erk1/2 knockout mice, we verified that MOS-ERK signal pathway inactivation in oocytes caused EEAF as human. The RNA sequencing data revealed that maternal mRNA clearance was disrupted in human mature oocytes either with MOS homozygous variant or with U0126 treatment, especially genes relative to mitochondrial function. Mitochondrial dysfunction was observed in oocytes with ERK1/2 deficiency or inactivation. In conclusion, this study not only uncovers biallelic MOS variants causes EEAF but also demonstrates that MOS-ERK signaling pathway drives human oocyte cytoplasmic maturation to prevent EEAF.
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