Pathways to an Egg for Fertilization

Pathways to an Egg for Fertilization
Paths to Egg to Fertilize - Sperm move towards their destination in response to a chemical slant. In an unrestricted setting of external fertilization (left), they do this deterministically. In a constrained environment of internal fertilization (right), they do so stochastically and with two different movement patterns. APS/KYWan/C. Cain

Mammalian sperm use a sophisticated stochastic navigation technique that depends on the rheological and chemical properties of the immediate environment. For each of us, fertilization is that unique and crucial moment when two gametes fuse and initiate an unstoppable series of events that result in the development of a new life. This method of reproduction has continued throughout the eukaryotic tree of life, from single-celled organisms to animals and plants, and is essential to promoting genetic diversity. The precise sequence of events in which gametes find each other in a complex and diverse landscape has puzzled scientists for over a century. The accepted theory argues that sperm move deterministically towards their egg targets.

Meisam Zaferani and Alireza Abbaspourrad of Cornell University have shown in a recent study that bull sperm use a specific biphasic (or biphasic) swimming style in response to chemotactic cues, which may be regulated by the rheological properties of the surrounding fluid. This discovery offers an intriguing hypothesis that sperm randomly pass through the complex boundaries of the female reproductive tract.

We imagine a sperm swimming stubbornly towards an immobile egg in its struggle for survival, and its flagella waving. Although attractive, this depiction of heroes is not always accurate. First, in many unicellular organisms such as ciliates and algae, both partners are motile. The challenge of fertilization in this case is physically enormous because it requires trying to hit a moving target while tackling the cacophony of background noise.

So what is the mechanism behind this search and capture process?

What differences are there between the species?

Stochastic or deterministic?

Fertilization can occur internally or externally as seen in the figure in nature.

For external fertilization in open water, marine invertebrate sperm must somehow find a distant egg and rely on weak biochemical cues produced by the egg to steer them in the right direction. In contrast, in mammals where fertilization is internalized, sperm cells respond to chemical cues. However, in order to overcome the challenging microarchitecture of the female reproductive tract and reach the oviduct, they must also change the rate of contraction of their flagella, during which they are often subjected to harsh competitive selection.

Depending on the situation and the preferred method of fertilization, a traveling sperm cell will therefore be subject to a variety of physical and molecular interactions.

With the exception of a few select species, and even then, for some molecules only involved in receiving and responding to signals, the precise functional link between environmental inputs and intrinsic flagellar kick and subsequent swimming trajectory is not yet fully understood. The pulse pattern can also be greatly influenced by a number of physical properties of the liquid medium such as viscosity, viscoelasticity and even ionic content.

Zaferani and Abbaspourrad utilized phase-contrast imaging and a controlled microfluidic environment to monitor how bull sperm responded to 4AP, a potent potassium channel blocker, in two viscosity regimes. The drug is supposed to copy the biological markers that the egg secretes.

The researchers found that as the concentration of 4AP increased, the sperm moved in increasingly tight circles within a viscoelastic buffer that mimics mammalian bodily fluids. This behavior has been described as "chiral" by the researchers. However, the sperms moved in a three-dimensional manner and along linear routes in a low-viscosity buffer without 4AP, which is absent in the viscoelastic scenario. Moreover, as the concentration of 4AP increased, the sperm became more active and lost directionality. This behavior has been classified as hyperactive by researchers. 4AP probably worked in both regimens by changing the flagellar dynamics and adjusting the asymmetry of the beat pattern.

The scientists created a model to account for the speed, rolling, and flagellar asymmetry of the chiral and hyperactive swimming of sperm.

Then, applying the model to the sperm observations, they extracted the statistical properties of the trajectories such as orientational persistence and diffusion. Interestingly, the rheological properties of the fluid had a significant influence on whether the dominant mobility pattern was chiral or hyperactive. Also, the effective diffusivity for both phenotypes decreased as the 4AP concentration increased. The transition from wobble to swimming, recently discovered in bacteria swimming in viscoelastic media, may be related to the significant suppression of three-dimensional rolling in the non-Newtonian regime. According to Zaferani and Abbaspourrad, the biphasic motility strategy of mammalian sperm can be tuned using a mix of biochemical and rheological cues by changing the mixing rate of the swimming trajectory and altering the route diffusivity.

They suggested that a stochastic search may be more successful in a geographically heterogeneous environment than a deterministic search in which the spiral course of the cell is progressively aligned to a stimulus from a constant, distant source.

When and how did sperm of various species diversify their way of navigation?

Early eukaryotes, nucleated single-celled animals, first showed signs of sexual reproduction in the fossil record more than 1 billion years ago. Small prokaryotes (unicellular organisms without a nucleus) whose small bodies are invaded by thermal noise are often associated with stochastic search techniques based on temporal comparisons, such as run-and-roll chemotaxis. Deterministic taxes are available to larger eukaryotes. There are, however, a few outliers.

For example, choanoflagellates, a eukaryote closely related to members of the animal kingdom, use a stochastic search technique to find areas with higher dissolved oxygen concentrations [9]. The research by Zaferani and Abbaspourrad highlights the need for additional comparative studies covering the entire eukaryotic tree of life.

However, sperm alone do not play a role in fertilization. Cells surrounding the oviduct contain cilia, or hair-like structures, that coordinate dynamic background flows to guide and sort sperm. The response of sperm to mechanical touch and viscosity gradients may also interact with chemokinetic responses. It is possible for the sperm to escape physical constraints with the help of the hyperactive mode, which requires sudden reorientations.

In conclusion, the stochastic chemokinetic behavior of sperm and other small eukaryotes represents a still unexplored search technique with theoretical and biomolecular underpinnings.


📩 13/06/2023 11:24