Alireza Abbaspourrad1

1, Yongkeun Joh Assistant Professor of Food Chemistry and Ingredient Technology, Cornell University, Ithaca, New York, United States

The fertilization process in mammals as sperm traverse towards the fertilization site where the oocyte has been released. In the case of marine animals and plants, which release gametes into the sea, the motion of sperm occurs in a vast aquatic environment. In contrast, the fertilization process of mammals happens inside a complex environment known as the “female reproductive tract”. The intriguing, multifaceted question is, how do healthy sperm naturally navigate the correct path towards the fertilization site? And concurrently, how does the female reproductive tract select for the best sperm while they move towards the oocyte. Since performing in vivo studies to answer these questions is difficult and faces many technical and ethical issues, designing in vitro environments that mimic at least one facet of female reproductive tract is vital.
In the last two decades, “microfluidics”, with its high and unprecedented precision of preforming studies on microswimmers and active matters in microenvironments, has enabled us to study the navigation strategies of mammalian sperm. Although the journey of mammalian sperm is many-sided and includes complex biological and chemical processes, studying the motion of sperm in microfluidic geometries, and under fluid flows that mimic the biophysical aspects of the sperm swimming channel in vivo, is critical. These studies will reveal new insight about the physical and fluid-mechanical clues provided by the female reproductive tract to facilitate sperm navigation towards the fertilization site.
The fluid-mechanical clues that enable mammalian sperm to swim along a correct path towards the fertilization site include the upstream swimming of the sperm in a simple, shear flow known as “rheotaxis”. Furthermore, the hydrodynamic interactions of sperm with nearby rigid boundaries is another navigation mechanism that is referred to as “boundary-dependent navigation”. We have performed studies on the fluid-mechanical navigation of the mammalian sperm as well as the influence of specific, geometrical features on the sperm locomotion.
To study the sperm navigation in a geometry that mimics the shape of “uterotubal junction”, which is a narrow junction at the beginning of fallopian tube, we designed a microfluidic stricture and studied the sperm locomotion under a simple shear flow. We discovered that such junctions select for highly motile sperm that can pass through the stricture while the slower sperm accumulate before the stricture. Therefore, a microfluidic stricture functions as a fluid-mechanical gate. The accumulation before stricture occurs in a hierarchical manner so that the competition is fiercest among sperm with the highest motility. To study the role of flagellar beating pattern on the sperm navigation, we first studied the flagellar beating pattern of sperm discovering a zeroth harmonic in the spatially asymmetric beating of the flagellum. This asymmetric beating creates a net torque and, thus, rotational components in the motion of sperm. We discovered that this zeroth harmonic, and asymmetric beating, impairs the boundary-dependent navigation while rheotaxis is less dependent on flagellar beating pattern.
To use our basic understanding of the sperm locomotion for such medical applications, we also have designed a microfluidic, rheotaxis-based sperm separation method. The microfluidic sperm separation techniques are sought-after for assisted reproductive technologies and infertility treatment as they are passive and operate without exertion of external forces. These efficient methods, accordingly, provide sperm with less DNA fragmentation. Our “microfluidic corral system” is a passive technique that only isolates progressively motile sperm with motilities higher than a tunable cut-off value.