Chen Yongzhe, Wang Zesong, Wu Yueren, He Wenbin, Du Juan, Cai Sufen, Gong Fei, Lu Guangxiu, Lin Ge, Dai Can
School of Basic Medical Science, Central South University, Changsha, China.
National Health Commission Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China.
Front Genet. 2021 May 19;12:690070. doi: 10.3389/fgene.2021.690070. eCollection 2021.
Empty follicle syndrome (EFS) is defined as the complete failure to retrieve oocytes after ovarian stimulation. Although several mutations in , and have been identified as genetic causes of EFS, its pathogenesis is still not well-understood. Whole-exome sequencing (WES) was employed to identify the candidate pathogenic mutations, which were then verified by Sanger sequencing. A study in CHO-K1 cells was performed to analyze the effect of the mutation on protein expression. Additionally, immunohistochemistry (IHC) staining was used to examine follicular development and zona pellucida (ZP) assembly in the ovary of an EFS patient. A novel heterozygous deletion in (c.565_579del[p.Thr189_Gly193del]) was identified in the EFS patient. It was inherited dominantly and resulted in significant degradation of the ZP3 protein. Oocytes with degenerated cytoplasm and abnormal ZP assembly were observed in follicles up to the secondary stage, and many empty follicle-like structures were present. We identified a novel mutation that expands the mutational spectrum associated with human EFS. We also showed the abnormal follicular development and ZP assembly of the EFS patient with the heterozygous ZP3 mutation, which provides new insights into the pathogenesis of EFS.
空卵泡综合征（EFS）被定义为卵巢刺激后完全未能获取到卵母细胞。尽管已确定 、 和 中的几种突变是EFS的遗传原因，但其发病机制仍未得到充分理解。采用全外显子组测序（WES）来鉴定候选致病突变，随后通过桑格测序进行验证。在CHO - K1细胞中开展了一项研究，以分析该突变对蛋白质表达的影响。此外，免疫组织化学（IHC）染色用于检查一名EFS患者卵巢中的卵泡发育和透明带（ZP）组装情况。在该EFS患者中鉴定出一种新的 杂合缺失（c.565_579del[p.Thr189_Gly193del]）。它呈显性遗传，并导致ZP3蛋白显著降解。在直至次级阶段的卵泡中观察到细胞质退化且ZP组装异常的卵母细胞，并且存在许多类似空卵泡的结构。我们鉴定出一种新的 突变，该突变扩展了与人类EFS相关的突变谱。我们还展示了具有杂合ZP3突变的EFS患者卵泡发育和ZP组装异常的情况，这为EFS的发病机制提供了新的见解。
