Researchers identify previously unknown mechanism of human fertilization.
IVF, or in vitro fertilization, currently has a 32 percent success rate, and couples for whom the procedure fails face the puzzling, disappointing reality that they can’t have a child of their own. Even when the process works, a high sperm-to-egg ratio is required, the opposite of what occurs in the body.
Now, a study from researcher a the University of Delaware has revealed for the first time that there is communication between the sperm and the fallopian tube that helps prepare the sperm for its big push into the egg. The team state that their findings could help couples struggling with infertility and may lead to the discovery of genes and gene products that cause infertility. The opensource study is published in the Journal of Biological Chemistry.
Previous studies show that once the egg is released from an ovary and enters the Fallopian tube, the hair-like cilia that line this tiny tube sweep the egg toward the uterus. While in the tube, the egg will either meet the sperm and be fertilized, which must happen within a 12- to 24-hour window of time, or fertilization will not occur and the egg will dissolve.
The current study identified previously unknown particles in the secretions from the fallopian tube that help the sperm get ready for its all-important drive into the end zone. They termed these bodies ‘oviductosomes’. Results show that hormones trigger the release of these oviductosomes, which are only 100 nanometers in diameter; the tiny cargo-filled sacs then attach to the sperm like decorations on a Christmas tree before the sperm fuses with the egg.
Data findings show that once these sacs are in place, they transfer proteins, including a ‘calcium clearance pump’, to the sperm for use when the time is right. The team observed that this calcium pump is required by the sperm just prior to fertilization, as well as in the early embryo. They explain that the sperm pumps out calcium and takes in hydrogen ions, which seems to give it that last push into the egg, and also is critical to starting the zygote’s life.
The current study used a high-powered, three-dimensional super-resolution microscope. The technology was used as it can illuminate what’s happening in a cell, right down to a single molecule. A mouse model was used as this is the closest genetic model to humans and has a much faster reproductive cycle. The researchers pre-labeled oviductosomes from a female mouse with a fluorescent dye and incubated them with the sperm, within an hour, the oviductosomes were fused to the sperm’s surface. The lab observed that after two to three hours, the oviductosomes continued to accumulate, primarily on the sperm’s head and the midpiece of its tail. The team explain that integrins, which are membrane receptors on both the sperm and the oviductosomes, helped to facilitate their bonding, along with fusion stalks on the sperm’s surface.
The team state that the discovery of these oviductosomes provides a window into the cargo being delivered by the female to the sperm. They go on to conclude that the implication is that they could improve IVF with this knowledge.
The researchers surmise that they have shown that these oviductosomes are carrying critical molecules that include proteins and nucleic acids such as RNA and also lipids. They go on to state that they hope their findings can be used as vehicles for improving fertility and the chances of producing healthy embryos and offspring. For the future the group are analyzing the protein-rich contents of the oviductosome cargo to index the next stage of the sperm’s journey and identify exactly what gives the sperm what it needs to penetrate the egg.
Source: University of Delaware