Biphasic Chemokinesis of Mammalian Sperm

The female reproductive tract (FRT) continuously modulates mammalian sperm motion by releasing various clues as sperm migrate toward the fertilization site. An existing gap in our understanding of sperm migration within the FRT is a quantitative picture of how sperm respond to and navigate the biochemical clues within the FRT. In this experimental study, we have found that in response to biochemical clues, mammalian sperm display two distinct chemokinetic behaviors which are dependent upon the rheological properties of the media: chiral, characterized by swimming in circles; and hyperactive, characterized by random reorientation events. We used minimal theoretical modeling, along with statistical characterization of the chiral and hyperactive trajectories, to show that the effective diffusivity of these motion phases decreases with increasing concentration of chemical stimulant. In the context of navigation this concentration dependent chemokinesis suggests that the chiral or hyperactive motion refines the sperm search area within different FRT functional regions. Further, the ability to switch between phases indicates that sperm may use various stochastic navigational strategies, such as run and tumble or intermittent search, within the fluctuating and spatially heterogeneous environment of the FRT.

Figure 1

Experimental characterization of sperm chiral motion. (a) Left: overlayed images acquired from the chiral motion in 5 seconds (frame rate $\sim 25\mathrm{frame}/\mathrm{s}$). Right: overlayed images acquired from the 4AP treated chiral motion in 5 seconds (frame rate $\sim 25\mathrm{frame}/\mathrm{s}$). (b) MSD of chiral motion (35 trajectories for each treatment). (c) Orientational autocorrelation of the chiral motion, with and without treatments. $\lambda$ is a coarse graining parameter (Fig. S2 [41]). (d) Effective diffusivity of the chiral motion vs the curvature of the circular path.

Figure 2

Experimental characterization of sperm hyperactive motion. (a) Sperm trajectories at treatments with 2.5 and 5.0 mM of 4AP. The average time between points is $\sim 0.08–0.1\mathrm{s}$ and trajectories are color coded according to the translational speed (scale on the top right: $100\mathrm{\mu }\mathrm{m}$). Box: sperm rolling (scale: $10\mathrm{\mu }\mathrm{m}$). (b) Probability distribution of reorientation angles. (c) MSD, (d) orientational autocorrelations, and (e) persistent length measured for the hyperactive phase. (25 trajectories for control and each treatment and ${}^{*}p$ value $<0.0001$).

Figure 3

(a) Effective diffusivity of the hyperactive phase vs translational speed. (b) Sperm treated with 5.0 mM 4AP exhibited detachments from the sidewall. One of the trajectories is color coded according to elapsed time. Diameter of chamber: $600\mathrm{\mu }\mathrm{m}$. (c) Same trajectory is color coded according to translational speed. $\varphi$ is the reorientation angle and $u^{*}$ is the normalized translational speed. Detachments from sidewall are marked with “$a$” and “$b$”. These detachments are caused by sharp reorientation events. Scale bar: 5 s. (d) Picture of sperm motion including progressive, chiral, and hyperactive phases.