A woman’s fertility depends on the growth and maturation of eggs (oocytes) within the follicle. Within these follicles, the oocyte is surrounded by granulosa cells, which provide essential nutrients, signaling molecules, and structural support for egg development. Communication between granulosa cells and oocytes occurs through thin cell extensions known as transzonal processes (TZPs) that physically connect the two cell types across the zona pellucida. Although TZPs were traditionally thought to be primarily actin-based structures, the role of microtubules within TZPs was poorly understood.
To better understand the contribution of microtubules to follicle development, a Japanese research group led by Professor Masamitsu Sato and Associate Professor Mika Toya from Waseda University and Kyoto University investigated the role of the microtubule-stabilizing protein Camsap3 in TZP tissue and granulosa cell-oocyte communication. The research team included Dr. Akihiro Aikawa, Dr. Takao Tsurumaki, Dr. Erina Kuranaga from Kyoto University, and Dr. Junya Ito from Azabu University. The study was made available online on April 28, 2026 and was published in the journal Volume 29, Issue 6. iscience June 19, 2026.
To investigate the functionality of Camsap3, researchers Kamsap 3-Knockout (KO) mice were generated and compared with wild-type mice. Fertility and ovulation were assessed through natural mating experiments and hormone-induced superovulation assays. Follicles at different developmental stages were examined using histological analysis, and super-resolution microscopy and immunostaining techniques were used to visualize the localization of TZPs, actin filaments, microtubules, and Camsap3. Additional experiments assessed granulosa cell apoptosis and proliferation, and follicular reconstitution assays were performed to measure the individual contributions of granulosa cells and oocytes to follicular development.
This study revealed several important findings. woman camsap 3-KO mice are completely infertile and fail to ovulate despite maintaining normal oestrous cycles, indicating that this defect is not hormonal in nature. Follicular development was disrupted during the transition from the secondary to antral phase, resulting in increased follicular degeneration and a significant reduction in mature Grafian follicles. Most surprisingly, super-resolution imaging demonstrated that over 80% of TZPs contain both microtubules and actin, overturning the long-held idea that TZPs are primarily actin-based structures.
Regarding the importance of this discovery, Mr. Sato said:Super-resolution microscopy reveals that microtubules connecting the oocyte and surrounding granulosa cells are present within the TZP and at a higher frequency than previously detected, highlighting the underestimated role of microtubules in oocyte-granulosa cell (GC) communication.“Loss of Camsap3 caused severe disruption of microtubules within TZPs, reducing the number of TZPs and resulting in the loss of specialized TNT-like TZPs that may facilitate the transport of large molecules and organelles such as mitochondria. As a result, communication between granulosa cells and oocytes was severely impaired, ultimately preventing proper follicle maturation and ovulation.”
Mr. Toya further emphasized the broader implications of the findings, saying:This study demonstrates that Camsap3 stabilizes microtubules within the TZP and reveals a molecular mechanism by which impaired communication between oocytes and granulosa cells causes infertility and follicular atresia.”
This discovery provides important insight into the cellular mechanisms underlying female fertility. This study expands our current understanding of follicle biology by identifying microtubules as important structural and functional components of TZPs and highlights Camsap3 as a key regulator of reproductive function. These findings may also help identify new targets for infertility diagnosis and treatment, while improving infertility symptoms. in vitro Follicle culture systems used in reproductive research and assisted reproductive technology.
In conclusion, this study revealed a previously underappreciated role for microtubules in follicle development and demonstrated that Camsap3-mediated microtubule organization is essential for granulosa cell-oocyte communication, successful ovulation, and maintenance of female fertility.
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Reference magazines:
Please send it to me, A. others. (2026) Camsap3-mediated microtubules maintain transzonal projections essential for soma-germ communication during mouse follicle maturation DOI: 10.1016/j.isci.2026.115911. https://www.cell.com/iscience/fulltext/S2589-0042(26)01286-1
