Molecular 'barcode' helps decide which sperm will reach an egg

A study in mice provides insights on the processes that determine which sperm will reach an egg to fertilise it, a discovery that may aid infertility research

ELIFE

Research News

 

IMAGE: THREE-DIMENSIONAL IMAGE SHOWING THE HEAD (GREEN) AND TAIL (RED) OF SPERM CELLS TRAVELLING TOWARDS THE FERTILISATION SITE (TO THE LEFT SIDE OF THE IMAGE) IN THE REPRODUCTIVE TRACT (BLUE CELLS)... view more 

CREDIT: LUKAS DED (CC BY 4.0)

A protein called CatSper1 may act as a molecular 'barcode' that helps determine which sperm cells will make it to an egg and which are eliminated along the way.

The findings in mice, published recently in eLife, have important implications for understanding the selection process that sperm cells undergo after they enter the female reproductive tract, a key step in reproduction. Learning more about these processes could lead to the development of new approaches to treating infertility.

"Male mammals ejaculate millions of sperm cells into the female's reproductive tract, but only a few arrive at the egg," explains senior author Jean-Ju Chung, Assistant Professor of Cellular & Molecular Physiology at Yale School of Medicine, New Haven, Connecticut, US. "This suggests that sperm cells are selected as they travel through the tract and excess cells are eliminated. But most of our knowledge about fertilisation in mammals has come from studying isolated sperm cells and eggs in a petri dish - an approach that doesn't allow us to see what happens during the sperm selection and elimination processes."

To address this challenge, Chung and colleagues, including lead author Lukas Ded, who was a postdoctoral fellow in the Chung laboratory when the study was carried out, devised a new molecular imaging strategy to observe the sperm selection process within the reproductive tract of mice. Using this technique, and combining it with more traditional molecular biology studies, the team revealed that a sperm protein called CatSper1 must be intact for a sperm cell to fertilise an egg.

The CatSper1 protein is one of four proteins that create a channel to allow calcium to flow into the membrane surrounding the tail of the sperm. This channel is essential for sperm movement and survival. If this protein is lopped off in the reproductive tract, the sperm never makes it to the egg and dies. "This highlights CatSper1 as a kind of barcode for sperm selection and elimination in the female reproductive tract," says Chung.

The findings, and the new imaging platform created by the team, may enable scientists to learn more about the steps in the fertilisation process and what happens afterwards, such as when the egg implants into the mother's uterus.

"Our study opens up new horizons to visualise and analyse molecular events in single sperm cells during fertilisation and the earliest stages of pregnancy," Chung concludes. "This and further studies could ultimately provide new insights to aid the development of novel infertility treatments."

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Reference

The paper '3D in situ imaging of female reproductive tract reveals molecular signatures of fertilizing spermatozoa in mice' can be freely accessed online at https://doi.org/10.7554/eLife.62043. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

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How to spot winning sperm: examine their racing stripes

YALE UNIVERSITY

Research News

 

Millions of sperm enter the race to fertilize, but only one wins the sprint to the egg.

Now Yale researchers have discovered that these winning sperm possess a few key molecular characteristics that differentiate them from those left behind, they report Dec. 1 in the journal eLife.

Sperm tails are lined with channels containing pores for entry of calcium which help sperm move through the female reproductive tract. Each pore of these calcium channels is comprised of four subunits, CatSper 1 through 4, which work together to serve functions such as controlling the mobility and navigation of the sperm.

Researchers playfully describe them as the sperm's racing stripes.

A team of Yale scientists led by Jean-Ju Chung, assistant professor of cellular and molecular physiology, found one of the subunits that form these racing stripes is critical in sperm selection for fertilization.

Using 3D molecular imaging and artificial neural network modeling, Chung's lab devised a way to visually track and quantify sperm in the reproductive tracts of female mice after mating. They discovered that the sperm which advanced from uterus to oviduct had the channels containing intact Catsper1 subunit. Other sperm likely lost functioning CatSper ion channels by losing intact CatSper1. These sperm become immobile and are left behind.

Sperm that make it far into the female reproductive tract share other characteristics: they tend to have already lost a cap-like structure called the acrosome in the sperm head, likely a prelude to fertilizing the egg.

The insights into molecular signatures of sperm and interactions within the reproductive tract may help inform new treatments for infertility or conversely, male birth control. Mutations have been found in the CatSper genes of infertile men and could be a target for fertility treatments. Since the CatSper channel is necessary for sperm to function, blocking it could lead to development of non-hormonal contraceptives with minimal side effects in both men and women, Chung said.

"Better understanding how the fittest sperm cells are selected and how those left are eliminated after fertilization in the female reproductive tract can improve current strategies for assisted reproduction," Chung said.

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Yale's Lukas Ded is lead author of the study, which was supported by the National Institutes of Health and funding from the Goodman-Gilman Scholar Award, which Chung won in 2015.