Sticky fallopian tube fluid holds key to causes of infertility

Researchers at Monash University’s Applied Microfluidics & Bioengineering Lab are researching the environment inside fallopian tubes hoping to shed light on female infertility.

Their new Nature Communications study has revealed a previously overlooked contributor to female infertility – the viscosity of fallopian tube fluid.

They found a thicker, sticky fluid environment promotes the growth of cells responsible for transporting eggs or embryos towards the uterus and even made them better at coordinating their movement.

This explains why flushing fallopian tubes with oil-based dye during X-ray imaging procedures significantly improves fertilisation outcomes when compared to the use of water-based dyes.

The findings open new avenues for research into therapeutic treatments for as-yet unknown causes of female infertility.

The fallopian tubes of the female reproductive system contain fluid that varies in viscosity both along the tube and throughout the menstrual cycle, ranging from as thin as water, to as thick as glycerine at ovulation.

The research looked at how the change in this viscosity influences the development and function of the cells that cover the inside of the fallopian tubes: secretory and ciliated epithelial cells (ECs).

Secretory ECs influence the chemistry and viscosity of the reproductive tract fluid, while ciliated ECs are covered in cilia, tiny hair-like structures that beat collectively to transport the egg or embryo along the fallopian tube.

An image showing the surface of epithelial cells in the fallopian tube. Some which are coloured pink have hair-like projections, others coloured purple are mostly round.
Coloured scanning electron micrograph (SEM) of the surface of a human fallopian tube. The epithelium consists of columnar cells, many of which have cilia (red). Coloured blue are the secretory cells with their microvilli projections. These cells secrete a substance that maintains a moist environment in the tube and may provide nutrients for the egg. Credit: STEVE GSCHMEISSNER / SCIENCE PHOTO LIBRARY / Getty Images

“They grow in patches, like a big island of ciliated cells,” says senior author Dr Reza Nosrati of the Department of Mechanical and Aerospace Engineering at Monash University, Australia.

“When these cells start to beat together, they start to form a metachronal wave … the wave that essentially helps to transport the egg.”

“We looked at how viscosity influences this behaviour … we show that it helps to get more ciliated cells closer to the site of fertilisation, and it also helps to slow down the movement of those cilia and kind of help them to coordinate and beat more collectively,” says Nosrati.

To mimic the environment of the fallopian tube, the team grew ECs in media of varying viscosity. They found that the more viscous media resulted in 4 times more ciliated epithelial cells and a 30% reduction in the beating frequency of the cilia.

It’s like difference between walking through water versus thick mud. The findings show that when this friction increases, “mechano-sensitive” ion channels on the cell’s surface experience more force.

“These are like gates that open and close, let the ion to go into or out of the cell,” says Nosrati.

“And one of the important ions is calcium, [which] controls the beating of the ciliated cells.

“More calcium influences how the cells metabolically behave and helped them to coordinate their beating and coordinate the cilia movement to essentially produce that more synchronised collective beating behaviour,” says Nosrati.

The increased ratio of ciliated to secretory ECs seen in the study is also known to peak along with tubal fluid viscosity at the time of ovulation.

Nosrati’s team will continue to research the impact of the fluid environment in the fallopian tubes on fertility.

“We’re going to start human models. We’ll start to look at … different geometry of the reproductive tract. Or, if you can get samples from patients of different backgrounds, how these types of behaviour are different in them,” he says.

“Then, maybe, we can explain some of the unknown causes of infertility or come up with some potential treatment.

“Of course, this is like 5-10 years down the road. It’s a very new research direction for us, but we’re excited to move in that direction.”

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