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Communication between oocytes and granulosa cells is essential for oocyte formation, dormancy, reawakening, and maturation. Researchers at University of Tsukuba have demonstrated that a protein complex called the exocyst complex plays a crucial role in this process. Using a mouse model, their investigations revealed that a deficiency in this complex causes female infertility.

Tsukuba, Japan—In many mammals, a limited number of oocytes are responsible for producing the next generation. Oocytes grow within follicles, which consist of an oocyte and the surrounding granulosa cells. Communication (crosstalk) between oocytes and granulosa cells is crucial for oocyte formation, dormancy, reawakening, and maturation. Oocytes express proteins c-KIT and GDF9, which play a vital role in this crosstalk. However, the mechanism of their transport within oocytes was previously unclear.

In this study, researchers found that a protein complex called the exocyst complex is essential for the proper transport of c-KIT and GDF9 within oocytes. Experiments using mice specifically deficient in the EXOC1 protein, a component of the exocyst complex, revealed the inhibition of oocyte reawakening and growth during follicular development and the suppression of granulosa cell proliferation. Further investigation showed that c-KIT and GDF9, which are normally present on the cell membrane or outside the cell, were abnormally accumulated in the cytoplasm of EXOC1-deficient oocytes. Similar results were observed in oocytes deficient in other exocyst complex proteins, such as EXOC3 and EXOC7.

These findings indicate that the exocyst complex is essential for the proper transport of c-KIT and GDF9 within oocytes and that a dysfunctional exocyst complex leads to female infertility.

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This work was supported by Scientific Research (B) (17H03566, to SM; 19H03142, to SM) and a Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area) (21H00224, to SM) from the Ministry of Education, Culture, Sports, Science, and Technology.

Original Paper

Title of original paper:

Exocyst complex component 1 (Exoc1) loss in dormant oocyte disrupts c-KIT and growth differentiation factor (GDF9) subcellular localization and causes female infertility in mice

Journal:

Cell Death Discovery

DOI:

10.1038/s41420-025-02291-5

Correspondence

Professor MIZUNO Seiya
Institute of Medicine, University of Tsukuba

Related Link

Institute of Medicine