Eggs Control Fertilization by Choosing Compatible Sperm

Egg and Sperm. Photo Credit: Ronald Megiddo

Sexual selection is responsible for bizarre displays of colors, anatomies, movements, and displays. From peacocks to bonobos, evolution is nothing if not unpredictable. But recent research suggests that females require more than wooing to successfully mate. In addition to foreplay, female’s eggs actually pose a series of challenges to sperm, sending them on a quasi-quest to reach fertilization, or perish trying.

What is this autonomous egg system and how did it come about?

Humans spend a considerable amount of time and energy choosing their partners, especially compared to our relatives in other living kingdoms. Evolutionarily however, our mating techniques originated in the ocean. For fertilization, our marine microscopic ancestors and their present-day predecessors released massive clouds of free-floating eggs and sperm into the ocean. These events, aptly called broadcast spawning, allow both marine invertebrates and vertebrates the potential for offspring, even when the proper partners are far away. For eggs and sperm to find one another would be seemingly impossible, and a great feat of random chance. Today however, a series of mutations provide instructions for gamete meet-and-greets. Modern free-floating eggs release chemical signals (like scents) to attract sperm. Since adults are unable to express pre-ejaculatory partner choices, females must rely on chemical variants (called chemoattractants) to assist with their blind dates. Sperm chemoattraction (in which eggs use chemicals to lure sperm to/away from them) allow eggs to preferentially recruit sperm from specific, and potentially more compatible males. In marine organisms, chemoattractants increase fertilization rates by raising the effective target sizes of gametes, maintaining species barriers through preferences for conspecific sperm, and allow for gamete-mediated mate choices.

We’ve established that chemical signaling (chemotaxis) greatly increases the efficacy of finding compatible gametes and consequent fertilization, but...

How do chemoattractants work?

In marine invertebrates, chemoattractants preferentially recruit sperm from specific, and usually more compatible, mates by remotely changing sperm swimming movements and behaviors. Sperm that are compatible with the egg have an easier time approaching it, as opposed to those that are not compatible. The egg thereby increases fertilization rates, embryo viability, and offspring survival, even in the absence of its parent.

It turns out that this process, although intended for the open ocean, persists in animals that rely on internal fertilization (including mammals that undergo fertilization in a uterus). In mice for instance, eggs are preferentially fertilized by sperm that are genetically unrelated to the female. Mammalian chemoattractants can even influence perceived mating capability by maximizing genomic compatibility between mates, selecting ideal genes, reinforcing partner decisions, and even by overriding pre-mate choices.

Do chemoattractants affect human mating?

In humans, mate choice continues after sexual activity through communication between the female reproductive system and the sperm. Like the chemotaxis utilized by our marine ancestors, females bias the sperm that they use, exerting a cryptic choice for on males during the paternity process. Current research suggests that human sperm are influenced by the chemical makeup of the follicular fluid surrounding the egg (which likely contains progesterone and perhaps other hormones). The chemical attractants, found in the follicular fluid, appear to favor specific sperm from distinct males. Under experimental conditions, IVF (in-vitro fertilization) patients’ sperm and eggs showed clear and repeated preference for certain partner pairings over others. In the presence of sperm from multiple males, one female’s follicular fluid consistently attracted sperm from one specific male, even when the egg was exposed to sperm from multiple males.

Imagine a series of females and males. For the sake of the example, we’ll give each a name and a color.

Females: Sally (yellow), Rita (blue), Lucy (green), Ellen (red)

Males: Harry (yellow), Tom (blue), Ricky (green), Adam (red)

When Sally’s egg is exposed to both Harry and Tom’s sperm, Harry’s sperm is most effective at finding the egg. When Sally’s egg is exposed to Harry and Ricky’s sperm, Harry’s sperm is again the best at reaching the egg. Against Adam, Harry’s sperm is also most effective. Perhaps Harry’s sperm are really good at finding eggs; to test this, we could expose Harry’s sperm to different eggs.

When Harry and Tom’s sperm are exposed to Rita’s egg, Tom’s sperm are the best at accessing the egg. This suggests that Harry’s sperm aren’t the fastest after all. Another iteration shows that Tom’s sperm are also better at reaching Rita’s egg, compared to Ricky’s. Against Adam, the result is the same. This leads us to wonder: Are Ricky and Adam’s sperm less fit than Harry and Tom’s?

In a race against Harry, Tom, and Adam’s sperm, Ricky’s sperm reach Lucy’s egg fastest and with the highest frequency. Ricky’s sperm are effective after all.

In the final combination, Adam’s sperm are closest to fertilizing Ellen’s egg. By now, it’s no surprise that different eggs pair well with different sperm. Continuing this pattern in petri dishes yields the following:

In our examples, the sperm and egg colors conveniently mirrored one another. In experimental conditions however, a different quality determines sperm-egg interactions.

Sperm swim preferentially towards their partner’s eggs most of the time, so long as the couple’s gametes are genetically compatible for immune defense.

To determine how human sperm know where to go, scientists took a hint from our marine ancestors. They examined the egg, sperm, and surrounding materials to determine if signals could get from one gamete to the next.

What caused this variation and how can we explain it?

In each egg scenario, the favorable sperm owner changed. All sperm were capable of reaching the egg, but each male’s gametes functioned best with a different egg. The egg, therefore, must change how sperm perform and behave using follicular fluid. It turns out that follicular fluid (darkest ring around the egg in the diagrams), doesn’t solely attract sperm, but actually chemically chooses which sperm to attract (and which to avoid). It is unclear however, how the egg exerts this power. Perhaps the follicular fluid alters the swimming physiology and behavior of human sperm, as it does in marine invertebrates. More research is needed to determine the mechanisms behind cryptic female choice.

Are there implications for humans?

The egg’s ability to exert post-mating sexual selection is a novel idea, but chemosensory-driven gamete interactions likely span the animal tree of life, providing widespread and autonomous egg-mediated mate choice (25 years of evidence in humans). Current research extends the traditional view that chemoattraction is solely responsible for increasing egg-sperm interactions in humans, instead highlighting a penultimate post-mating sexual selection strategy.

In IVF patients, the egg-attracted sperm, and consequent female-male interactive effects, raised the compatibility of genomic compatibility and fertilization. Sperm swim preferentially towards their partner’s follicular fluid most of the time, reflecting that the couple’s gametes were genetically compatible for immune defense (at the major histocompatibility complex (MHC)), although this assumption remains controversial.

When sperm got lost or unsuccessfully made it to the follicular fluid surrounding the egg, the egg and sperm donors often exhibited similar genetic information, a perfectly common companion trait, but a biological no-no for mating. Alternatively, in some infertility cases, lost sperm may be explained by a lack of chemical signaling or receival by the gametes. If the signal is not produced or if the signal cannot be received, the sperm and egg will not meet, regardless of genetic compatibility.

In the absence of a single comprehensive rationale, scientists need more information. Study into female-male interactive effects and the mechanisms between gamete chemical communication will assist in clarifying what influences sperm grouping in the follicular fluid. Such advances may aid in the development of new diagnosis and treatment of unexplained infertility, increased efficacy and safety of assisted reproductive treatments, and more accurate assessments of genomic compatibility in potential mates. The medical community is expected to weigh in on the bioethical implications of such procedures and their implications.

 

Are eggs truly autonomous? Is judging genetic compatibility ethical? What would you do with these findings? What should I write about next?

Leave your answers in the comments section below. Spread the conversation by sharing, if you like.

 

© 2020 Sabrina L. Groves. Creative Commons Attribution-Noncommercial 4.0 International License.