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Updated: Jan 27, 2026
Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
A pannexin 1 channelopathy causes human oocyte death
Qing Sang1, Zhihua Zhang2, Juanzi Shi3
1Zhongshan Hospital, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. wangleiwanglei@fudan.edu.cn kuangyanp@126.com sangqing@fudan.edu.cn.
Abstract:
Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms three species, GLY0, GLY1, and GLY2. Here, we describe four independent families in which mutations in PANX1 cause familial or sporadic female infertility via a phenotype that we term "oocyte death." The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.
Insights
Mutations in Pannexin 1 (PANX1) cause female infertility by disrupting oocyte development. This research identifies a new genetic cause of infertility and a potential therapeutic target.
Area of Science:
- Cellular Biology
- Genetics
- Reproductive Medicine
Background:
- Connexins and pannexins are key protein families involved in cellular communication.
- Pannexin 1 (PANX1) is a glycosylated channel protein forming GLY0, GLY1, and GLY2 species.
Observation:
- Four families with mutations in PANX1 exhibit a phenotype termed 'oocyte death,' leading to infertility.
- These mutations affect PANX1 glycosylation, subcellular localization, and channel activity, including ATP release in oocytes.
Findings:
- Mutant PANX1 GLY1 species are identified.
- Overexpression of a patient-derived mutation in mice replicates the human oocyte death phenotype and infertility.
- PANX1 mutations are directly linked to a specific form of female infertility.
Implications:
- PANX1 plays a critical role in human oocyte development.
- This study provides a genetic basis for a subtype of female infertility.
- PANX1 presents a potential therapeutic target for treating this infertility.
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