Women’s fertility is influenced not only by the quality of their eggs but also by the interactions between somatic cells in the ovary. A recent study by TalTech researchers, conducted in international collaboration, provides a better understanding of how different ovarian cells exchange information. This knowledge is crucial for advancing fertility treatments.
Tiny messengers of cells
In living organisms, cells are constantly sending and receiving signals. The most common form of communication is through chemical signals, such as hormones. In many body fluids, cells use extracellular vesicles to exchange information. These nanoscale particles act like courier packages, through which cells send messages to each other, influencing their activity, shape, or behaviour. Vesicles contain various molecules, including short RNAs, which can alter the behaviour of neighbouring cells. It is known that cells release different vesicles depending on their developmental stage and condition, so vesicles reflect what is happening inside the cells.
Vesicles as influencers of egg development
Researchers at TalTech’s Department of Chemistry and Biotechnology, in collaboration with researchers from the University of Helsinki and the Tallinn-based company HansaBioMed Life Sciences, investigated how vesicles affect the environment of the developing egg and ovarian function. The egg grows inside a follicle – a fluid-filled sac that provides an optimal environment for its growth together with its supporting granulosa cells. Extracellular vesicles float within this follicular fluid surrounding the egg.
According to TalTech PhD student and co-author of the study Inge Varik extracellular vesicles are known to vary in size, density, surface components, appearance, and content, but they are usually studied as a mixture of these different subtypes. “We wanted to determine whether this approach is sufficient or whether different vesicle subtypes should be analysed separately to better understand the information they carry and their impact on ovarian cells.”
Different messages, different effects
The study compared the effects of small (100 nanometres in diameter) and large (300 nanometres in diameter) vesicles on granulosa cells. Granulosa cells are supporting cells within the follicle that produce steroid hormones and help the oocyte mature, thereby regulating follicle development and fertility.
The results revealed distinct effects. Smaller vesicles had a broad impact on gene expression, signal transduction, and the organization of the extracellular environment. Larger vesicles, on the other hand, had a more modest effect on gene expression but significantly increased testosterone production.
Agne Velthut-Meikas, head of the Reproductive Biology research group and co-author of the study, emphasizes: “Our work shows that communication within the follicle is far more complex than previously thought. Each vesicle carries very specific and important information. We found that large vesicles contain significantly more piRNA-type short RNA molecules, the role of which in ovarian steroid-producing granulosa cells is still unclear. However, these molecules are known to be important for egg development.”
Unlocking the secrets of fertility
Unlocking the secrets of fertility
Communication between cells plays a crucial role in follicle development. When this communication is disrupted – due to aging, environmental factors, or disease – it can affect the female fertility. “This discovery provides a strong foundation for our ongoing research, in which we are examining vesicles from women with fertility issues and their effects on cells,” explains Varik.
The study has another potentially valuable application. Extracellular vesicles could, in the future, serve as biomarkers that provide precise information about the state of cells and the entire organism. A woman’s fertility – specifically the quality of her eggs – could be addressed based on the piRNA profiles detected in vesicles within the follicular fluid. “If we can identify reliable vesicle-based biomarkers that reflect egg quality or the ovarian response to fertility treatment, it would lead to major advances in personalized medicine,” says Velthut-Meikas.
The study, „Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells“, was published in the prestigious Journal of Extracellular Vesicles.
The study, „Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells“, was published in the prestigious Journal of Extracellular Vesicles.