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A new study on the relationship between fluid viscosity and cellular function in the reproductive tract offers a new perspective on how fluid dynamics within the tract might influence fertility, particularly in cases where abnormal viscosity may be present.
Infertility affects 1 in 6 couples worldwide, accounting for ~15% of people of reproductive age. Men and women contribute equally to infertility issues, each responsible for about 40% of cases, with the remaining 20% attributed to combined factors or unknown causes. Common causes include hormonal imbalances, ovulation disorders, low sperm count, or structural issues within the reproductive organs.
Infertility is not just a medical condition but also has significant emotional, psychological and social impacts. Many individuals experience feelings of inadequacy, frustration and grief, compounded by societal pressures to have children. Cultural background can further intensify this burden on infertile couples. This often leads to increased stress and anxiety. The financial burden of fertility treatments (up to $10 000–$15 000 per in vitro fertilisation or intracytoplasmic sperm injection treatment cycle in Australia) adds another challenge, as these options are costly and often inaccessible for many couples.
Understanding the fallopian tube
A key difficulty in advancing infertility treatments lies in understanding the female reproductive system, particularly the oviduct (fallopian tube). The oviduct’s location poses significant challenges for direct study and observation. Understanding its microenvironment — fluid flow, biochemical signals and physical cues — is essential for understanding reproduction and improving assisted reproduction outcomes. Among all contributing factors, the role of tubal fluid viscosity and its potential influence on the development and function of the female reproductive tract has likely been overlooked for a long time.
The rheological properties of the female reproductive tract environment vary across time and location, but little is known about how these changes influence cellular behaviour. We published the first study exploring the role of elevated tubal fluid viscosity on the behaviour of epithelial cells, particularly their cilia formation and coordination. Our goal was to determine whether increased viscosity impacts the development and function of the epithelial cells that line the reproductive tract, and how this might influence the ratio of ciliated (cells with hair-like structures) to secretory epithelial cells. The proportion of these two cell types varies along the tract, regulating the tubal fluid flow via secretions or cilia movement, with more ciliated cells near the site of fertilisation, to collectively facilitate fertilisation and successful transport of eggs and embryos.
Studying viscosity
To simulate the conditions in the reproductive tract, we cultured epithelial cells in media with a viscosity ranging from 1 mPa·s (similar to water) to 200 mPa·s (similar to maple syrup). Using microscopy, we observed epithelial cell development, focusing on how the increased viscosity influenced ciliation and the coordination of cilia movement. We used calcium imaging and staining techniques to monitor intracellular changes in calcium levels and mitochondrial function to explain the underlying intracellular mechanisms of cell responses to elevated viscosity.
Our results showed a marked response to elevated viscosity. Ciliation increased by four-fold, and the cilia beating frequency decreased by 30%, suggesting that higher viscosity promotes the formation of cilia but slows their movement. Importantly, we observed that the cilia exhibited a more coordinated beating pattern, facilitating the creation of metachronal waves – wave-like movements created when cilia move in a rhythmic pattern. Metachronal waves are essential for transporting eggs and embryos through the reproductive tract, and our study highlights the crucial role of tubal viscosity in facilitating their formation and enhancing the efficiency of egg and embryo transport within the tract. This also underscores how the absence of such a high viscosity environment may lead to abnormal tissue development in vivo or potentially contribute to infertility.
The coordination of beating cilia is triggered by the activation of the TRPV4 channel under viscous loading, which increases intracellular calcium levels and decreases mitochondrial membrane potential. This helps the cells maintain their energy levels and viability under challenging conditions. Therefore, these changes likely modulate energy production levels in epithelial cells to sustain their function.
A fresh perspective
The strength of this study lies in its novel focus on the relationship between fluid viscosity and cellular function in the reproductive tract. For clinicians, these findings offer a new perspective on how fluid dynamics within the tract might influence fertility, particularly in cases where abnormal viscosity may be present. However, it’s important to note that this study was conducted using an in vitro model, which may not fully replicate the complexity of the in vivo environment. Further research, potentially using animal models, could provide more comprehensive insights into how these findings translate to clinical practice and might influence fertilisation outcomes, for example, by switching to high viscosity culture media.
Moreover, our work offers fresh perspectives on embryo–endometrium layer interactions, potentially elucidating infertility issues related to ciliogenesis. For example, the fertility-enhancing effect of oil-based tubal flushing media, a common clinical practice that lacks a well understood basis, might be explained by the findings of our study.
We would also like to emphasise the importance of providing greater mental and emotional support for individuals undergoing fertility treatments. Infertility is not just a physical issue but also a deeply emotional one. Health services should ensure that counselling and mental health resources are integrated into fertility clinics, helping patients navigate the emotional complexities of infertility. By addressing these areas, we can provide more effective, accessible and compassionate services for those affected.
About the authors
Dr Reza Nosrati is an NHMRC Fellow, senior lecturer, and the director of the Applied Microfluidics and Bioengineering (AMB) Lab at Monash University.
Dr Melati Suhaila Abdul Halim is a postdoctoral research fellow in biomedical engineering at Monash University.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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