Prediction of Sperm Progression in Three Dimensions Using Rapid Optical Imaging and Dynamic Mechanical Modeling

Abstract

We present a multidisciplinary approach for predicting how sperm cells with various morphologies swim in three-dimensions (3D), from milliseconds to much longer time scales at spatial resolutions of less than half a micron. We created the sperm 3D geometry and built a numerical mechanical model using the experimentally acquired dynamic 3D refractive-index profiles of sperm cells swimming in vitro as imaged by high-resolution optical diffraction tomography. By controlling parameters in the model, such as the size and shape of the sperm head and tail, we can then predict how different sperm cells, normal or abnormal, would swim in 3D, in the short or long term. We quantified various 3D structural factor effects on the sperm long-term motility. We found that some abnormal sperm cells swim faster than normal sperm cells, in contrast to the commonly used sperm selection assumption during in vitro fertilization (IVF), according to which sperm cells should mainly be chosen based on their progressive motion. We thus establish a new tool for sperm analysis and male-infertility diagnosis, as well as sperm selection criteria for fertility treatments.

Dynamic 3D Modeling for Human Sperm Motility through the Female Cervical Canal and Uterine Cavity to Predict Sperm Chance of Reaching the Oocyte

“…We used the 3D geometrical models of normal and abnormal sperm cells developed in our previous study [19] and tested them only for swimming in an infinite medium. In this previous study, we built a numerical mechanical sperm model based on ultra-rapid dynamic 3D imaging experimental results of sperm cells obtained by our group [20].…”

“…A normal-morphology sperm cell swimming in a fluid was acquired with our dynamic interferometric computer tomography method at a spatial resolution of 0.5 microns, achieving both the retrieval of the 3D refractive index profile of the sperm head and the detailed 4D localization of the thin, highly dynamic sperm flagellum. The acquisition duration was 1 s. Based on these experimental results, in [19], the dynamic geometrical sperm model was built, and we could then predict the swimming patterns for hours. In this previous work, we tested sperm cells that were only swimming in an infinite medium, which does not necessarily predict how sperm would behave in a woman's body.…”

“…Here, the normal and abnormal sperm models were considered to be hyperactivated sperm models. The 3D hyperactivated beating patterns of the different models were created by increasing the dynein sliding forces applied to the sperm models from a previous study [19]. The movement characteristics of the hyperactivation mode are represented by the flagellar amplitude, flagellar beat frequency, and straight-line velocity of the sperm models [37][38][39] (see Video S2).…”

“…The models were assumed to be uncompressible materials with uniform mechanical properties for all components, such as density. Since the cell head is the major component by weight, changing the density of the components is not expected to significantly affect the swimming behavior [19].…”

“…We used 3D geometrical models of normal and abnormal sperm cells. The sperm cell models, including the full 3D sperm geometry, were constructed based on our previous experimental rapid optical acquisition method for individual human sperm cells during 3D movement [19,20]. The pathological sperm models include typical frequent defects in the sperm's head and flagellum morphologies, which are based on real-world sperm pathologies according to the WHO 2021 guidelines [21].…”