ZP1 mutations are associated with empty follicle syndrome: evidence for the existence of an intact oocyte and a zona pellucida in follicles up to the early antral stage. A case report
ZP1 mutations are associated with empty follicle syndrome: evidence for the existence of an intact oocyte and a zona pellucida in follicles up to the early antral stage. A case report
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DOI：
10.1093/humrep/dez174
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发表时间：
2019-11-01
影响因子：
6.1
通讯作者：
Lin, Ge
中科院分区：
文献类型：
--
作者：
Dai, Can;Chen, Yongzhe;Lin, Ge
空卵泡综合征(EFS)是指卵巢刺激后卵母细胞完全无法取回。尽管LHCGR和ZP3被确定为致病基因，但这些患者的卵母细胞发生了什么仍然不清楚，EFS的发病机制也仍然不清楚。在这里，我们确定了6个与EFS和女性不孕症相关的新的ZP1突变，这些突变是在5个不相关的家族中隐性遗传的。在CHO-K1细胞中的研究表明，这些突变导致ZP1蛋白的降解或截断。卵巢连续切片免疫组织化学结果显示，腔前卵泡结构正常，但卵母细胞周围有较薄的ZP，缺乏ZP1。在正常的卵丘-卵母细胞复合体组织中，有腔卵泡也有缺陷，这使我们推测ZP1的缺失可能导致卵母细胞退化或在卵泡穿孔过程中增加卵母细胞的脆性，最终导致EFS。据我们所知，这是第一个提供形态学证据的研究，表明EFS患者腔前卵泡发育正常，ZP组装异常。我们的数据为我们更好地了解ZP1在人类ZP组装和卵泡发生中的生物学功能提供了更好的信息，并为EFS的发病机制和可能的治疗开发提供了新的见解。
Empty follicle syndrome (EFS) is the complete failure to retrieve oocytes after ovarian stimulation. Although LHCGR and ZP3 were identified as causative genes, it is still unclear what happens to these patients' oocytes, and the pathogenesis of EFS remains obscure. Here, we identified six novel ZP1 mutations associated with EFS and female infertility that was inherited recessively in five unrelated families. Studies in CHO-K1 cells showed that these mutations resulted in either degradation or truncation of ZP1 protein. Immunohistochemistry using ovarian serial sections demonstrated that all preantral follicles had normal architecture, but with a thin ZP, lacking ZP1, surrounding the growing oocytes. The antral follicles were also defective in normal cumulus-oocyte complex organisation, leading us to speculate that the lack of ZP1 might lead to oocyte degeneration or increased fragility of the oocyte during follicular puncture, ultimately resulting in EFS. To our knowledge, this is the first study that presents morphological evidence showing normal preantral folliculogenesis with abnormal ZP assembly in EFS patients. Our data provides a better understanding of the biological functions of ZP1 in human ZP assembly and folliculogenesis and gives new insights into the pathogenesis of EFS and possible therapeutic developments.