In a world-first breakthrough, Monash University researchers have discovered how the curvature of the female fallopian tube plays a significant role in sperm guidance, behaviour changes and subsequent fertilisation.
The study, published in the prestigious Nature Communications, shows strong evidence that the interaction of sperm with the curved epithelial tissue in the fallopian tube provides guidance and triggers behavioural changes to stimulate capacitation – a physiological change in sperm to enable fertilisation success.
This discovery provides new opportunities for better understanding and treating male infertility worldwide. Infertility affects approximately 15 per cent of couples, or 48 million people, globally.
The research team, led by Dr Reza Nosrati and Professor Adrian Neild from Monash University’s Department of Mechanical and Aerospace Engineering, used droplet microfluidics to study sperm interactions with the soft curved interfaces of the reproductive tract, closely mimicking the mechanical properties of folded epithelial tissue within the female fallopian tube.
The natural selection process, in vivo, is mainly achieved in the female fallopian tube, where anatomical features and physiological conditions guide the sperm to the site of fertilisation.
The fallopian tube is lined with a highly complex folded epithelium surrounding a lumen that progressively narrows towards the egg. The mechanical properties of this tissue is considerably different to the rigid flat surfaces in common laboratory dishes or microfabrication materials that are six orders of magnitude stiffer.
To counter this experimental challenge, Dr Mohammad Reza Raveshi, a research fellow at Monash University, encapsulated individual sperm in droplets with their radius closely mimicking the curvature and mechanical properties of folded epithelial tissue in vivo.
“As the sperm get closer to the egg, the curvatures of the folds in the female fallopian tube increases as in smaller droplets, but the role of this geometrical complexity on sperm motion was yet to be understood,” Dr Nosrati said.
“We show that this geometrical change transforms sperm behaviour from a ‘progressive’ to an ‘attacking’ swimming mode, which is essential for capacitation and fertilisation.”
Dr Raveshi said the study indicates that sperm exhibit a greater tendency to attack and swim in contact with the surface at higher curvatures, while at lower curvatures the sperm navigate along the interface. Sperm in the ‘attacking’ mode swim about 33 per cent slower, and spend about twice the time at the interface than those sperm in the ‘progressive’ mode.
“This aggressive attacking mode and the physical contact between sperm and the epithelial tissue are essential for sperm capacitation and fertilisation competence closer to the site of fertilisation,” Dr Nosrati said.
“This is a highly dynamic and perfectly timed response mechanism in sperm, triggered by the natural anatomy of the female fallopian tube, to facilitate natural fertilisation.”
Professor Neild said in a free volume of fluid, with no guidance, sperm swim aimlessly.
“However, the fallopian tube anatomy offers guidelines to resolutely lead the sperm towards the egg, and creates a change in their behaviour which triggers capacitation, this is a remarkable transition from aimless motion to a highly directed movement,” Professor Neild said.
“From the biological perspective, our findings demonstrate the role of changes in the female fallopian tube geometry to alter sperm motion from a faster surface aligned locomotion in distal regions and the utero-tubal junction to a prolonged physical contact with the epithelial tissue close to the egg.”
Dr Nosrati said these findings provided additional insights into how to better understand and treat male infertility globally.
“Our research into how surface curvature can be used to guide the locomotion for sperm selection applications or to increase surface interactions for understanding sperm attachment and detachment mechanisms could be of benefit to couples struggling with infertility across the world,” said Dr Nosrati.
Dr Reza Nosrati and Professor Adrian Neild (Department of Mechanical and Aerospace Engineering, Monash University) led the study titled ‘Curvature in the reproductive tract alters sperm-surface interactions’. It can be found at https://doi.org/10.1038/s41467-021-23773-x
Research support was provided by Dr Mohammad Reza Raveshi and Melati Abdul Halim (Department of Mechanical and Aerospace Engineering, Monash University), Sagar Agnihotri (Mechanical and Aerospace Engineering / IITB-Monash Research Academy Bombay), and Professor Moira O’Bryan (formerly, School of Biological Sciences, Monash University, and currently Dean of Science at the University of Melbourne).