A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrest
Abstract Background Ovulatory dysfunction and oocyte maturation arrest are among the common causes of female infertility, but the genetic etiology of these phenotypes is not well understood. The ZP3 gene is responsible for coding the oocyte zona pellucida (ZP), and ZP3 mutation clinically manifests...
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BMC
2025-06-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-025-01706-2 |
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| author | Yingxue Liu Guanghui Yuan Yameng Hui Xiaoxiao Wang Jiashan Li Jiao Zhuang Huaiqian Dou Linfang Han Duan Li Cuifang Hao |
| author_facet | Yingxue Liu Guanghui Yuan Yameng Hui Xiaoxiao Wang Jiashan Li Jiao Zhuang Huaiqian Dou Linfang Han Duan Li Cuifang Hao |
| author_sort | Yingxue Liu |
| collection | DOAJ |
| description | Abstract Background Ovulatory dysfunction and oocyte maturation arrest are among the common causes of female infertility, but the genetic etiology of these phenotypes is not well understood. The ZP3 gene is responsible for coding the oocyte zona pellucida (ZP), and ZP3 mutation clinically manifests as abnormal zona pellucida or empty follicle syndrome. Nevertheless, its role in the process of ovulation and maturation of oocytes has rarely been reported. Case presentation In our study, we performed whole-exome sequencing in a 26-year-old proband with ovulatory dysfunction and oocyte maturation arrest, and we identified a novel heterozygous mutation in ZP3 (NM_001110354.1: c. 662 C > T, p.Pro221Leu), which is located within the ZP domain. The effects of the mutation were investigated through in vitro studies in HeLa cells, which revealed that the mutation resulted in a significant decrease in ZP3 protein levels. Additionally, the maturity of oocytes obtained from the patient with ZP3 mutation was significantly improved through the dual trigger treatment protocol, and the proband ultimately had a successful live birth. Conclusions Our findings expanded the pathogenetic spectrum of the ZP3 gene, which provided insights for treating patients with ovulatory dysfunction and oocyte maturation arrest related to ZP3 mutations. Clinical trial number Not applicable. |
| format | Article |
| id | doaj-art-98b48e14b26841e5bbd089a50e4f543f |
| institution | DOAJ |
| issn | 1757-2215 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-98b48e14b26841e5bbd089a50e4f543f2025-08-20T03:10:35ZengBMCJournal of Ovarian Research1757-22152025-06-0118111010.1186/s13048-025-01706-2A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrestYingxue Liu0Guanghui Yuan1Yameng Hui2Xiaoxiao Wang3Jiashan Li4Jiao Zhuang5Huaiqian Dou6Linfang Han7Duan Li8Cuifang Hao9Center for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityCenter for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityQingdao Central Hospital, University of Health and Rehabilitation SciencesCenter for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityGenetic Testing Center, Women and Children’s Hospital, Qingdao UniversityCenter for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityCenter for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityCenter for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityCenter for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityCenter for Reproductive Medicine, Women and Children’s Hospital, Qingdao UniversityAbstract Background Ovulatory dysfunction and oocyte maturation arrest are among the common causes of female infertility, but the genetic etiology of these phenotypes is not well understood. The ZP3 gene is responsible for coding the oocyte zona pellucida (ZP), and ZP3 mutation clinically manifests as abnormal zona pellucida or empty follicle syndrome. Nevertheless, its role in the process of ovulation and maturation of oocytes has rarely been reported. Case presentation In our study, we performed whole-exome sequencing in a 26-year-old proband with ovulatory dysfunction and oocyte maturation arrest, and we identified a novel heterozygous mutation in ZP3 (NM_001110354.1: c. 662 C > T, p.Pro221Leu), which is located within the ZP domain. The effects of the mutation were investigated through in vitro studies in HeLa cells, which revealed that the mutation resulted in a significant decrease in ZP3 protein levels. Additionally, the maturity of oocytes obtained from the patient with ZP3 mutation was significantly improved through the dual trigger treatment protocol, and the proband ultimately had a successful live birth. Conclusions Our findings expanded the pathogenetic spectrum of the ZP3 gene, which provided insights for treating patients with ovulatory dysfunction and oocyte maturation arrest related to ZP3 mutations. Clinical trial number Not applicable.https://doi.org/10.1186/s13048-025-01706-2Oocyte maturation arrestOvulatory dysfunctionZP3 mutationWhole-exome sequencingDual trigger |
| spellingShingle | Yingxue Liu Guanghui Yuan Yameng Hui Xiaoxiao Wang Jiashan Li Jiao Zhuang Huaiqian Dou Linfang Han Duan Li Cuifang Hao A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrest Journal of Ovarian Research Oocyte maturation arrest Ovulatory dysfunction ZP3 mutation Whole-exome sequencing Dual trigger |
| title | A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrest |
| title_full | A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrest |
| title_fullStr | A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrest |
| title_full_unstemmed | A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrest |
| title_short | A novel mutation in ZP3 causes human ovulatory dysfunction and oocyte maturation arrest |
| title_sort | novel mutation in zp3 causes human ovulatory dysfunction and oocyte maturation arrest |
| topic | Oocyte maturation arrest Ovulatory dysfunction ZP3 mutation Whole-exome sequencing Dual trigger |
| url | https://doi.org/10.1186/s13048-025-01706-2 |
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