Fertility Mystery Solved With Discovery of Protein Key

Infertility can be caused by a number of factors, including (but not limited to) DNA damage, chromosomal aberrations, hormonal conditions, age-related factors, and environmental factors. Some infertility conditions are specific to females, some to males, and some arise because of a combination of conditions in the male and female partners. Approximately 12 steps are involved in thoroughly investigating the cause of infertility in couples. In research published this week in Nature, with Dr. Enrica Bianchi of the Wellcome Trust Sanger Institute in Cambridge, UK as the lead author, scientists have moved closer to solving the mystery of fertility with the discovery of a protein that is key to the interaction of sperm and egg.

Because fertility is such a monumentally important topic, much research has been done on it. An early key to this mystery was discovered in 2005, when researchers found a protein present on the sperm’s surface that recognizes the egg, thereby enabling fusion to form an embryo. They named it “Izumo,” which is Japanese for “marriage shrine.” In today’s study, the research team is reporting the discovery of a cognate protein on the egg’s surface that binds Izumo: they named it Juno, after the Roman fertility goddess. The research study also confirmed that the binding of Izumo to Juno is the first step in the process of egg and sperm fusion, without which fertilization cannot take place. This particular interaction was difficult to pin down, because the binding between Izumo and Juno is low-affinity (i.e. their binding is quite weak). After the egg is fertilized, it rids itself of the remaining Juno protein on its surface within 40 minutes, so as to prevent more sperm from binding: if more than one sperm fused with the egg, the resulting zygote would have too many chromosomes, and would thus be inviable.

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In order to perform the experiment, the research team took the already-characterized Izumo protein, and developed an artificial version of it, to see what it bound to on a mouse egg. They used an assay called AVEXIS, which is designed to identify weak and transient interactions between receptors and the ligands they bind to. In this way, they found a folate receptor called Folr4, which they renamed Juno.

To prove that Juno was essential to female fertility, the research team created genetically modified mice that lacked the Juno protein on their eggs. The eggs of these mice did not fuse with sperm, and the mice were infertile. To complete their understanding of the interaction of Izumo and Juno, the researchers genetically modified male mice that lacked Izumo; these mice were then shown to be infertile.

This research is significant because it offers a shortcut through the many steps involved in treatment of infertility. Eggs and sperm of couples experiencing difficulty conceiving can be genetically screened to determine if their Izumo and Juno proteins are structured correctly. If it is established that these proteins are defective, couples can go directly to a procedure called “ICSI” for intracytoplasmic sperm injection, in which a sperm is directly injected into an egg, using an extremely fine needle. Dr. Gavin Wright, who leads the Institute’s Cell Surface Signalling Laboratory, hopes that the discovery of this key protein interaction will solve at least one fertility mystery, and allow improvements to fertility treatments as well as contraceptives.

Frequently Asked Questions

What is the Juno protein and why is it important for fertility?

Juno is a protein discovered on the surface of eggs that binds with a sperm protein called Izumo, enabling fertilisation to occur. This discovery by UK researchers at the Wellcome Trust Sanger Institute in Cambridge helps explain why some couples struggle to conceive, as problems with this protein interaction could be a previously unknown cause of infertility.

Could problems with the Juno protein be causing my infertility?

It's possible that issues with the Juno protein could contribute to unexplained infertility, which affects around 1 in 7 UK couples. If you've been trying to conceive for over a year (or 6 months if you're over 35), speak to your GP about a referral for fertility investigations, as NHS guidelines recommend exploring multiple potential causes.

Will this discovery lead to new fertility treatments on the NHS?

While this research is groundbreaking, it may take several years before it translates into clinical treatments available through the NHS or private clinics. However, understanding the Juno-Izumo interaction could eventually lead to new diagnostic tests or treatments for couples with unexplained infertility, potentially improving success rates for IVF and other assisted conception meth

How do I get referred for fertility testing through my GP?

According to NICE guidelines, you should see your GP if you haven't conceived after 12 months of regular unprotected intercourse, or sooner if you're over 36 or have known fertility concerns. Your GP can arrange initial tests and refer you to a fertility specialist, though waiting times and CCG funding criteria vary across different areas of England.

What tests are done to investigate infertility in the UK?

NHS fertility investigations typically include blood tests to check hormone levels and ovulation, semen analysis for male partners, and scans to examine the womb and fallopian tubes. According to researchers, there are approximately 12 steps involved in thoroughly investigating infertility causes, and your fertility clinic will work through these systematically based on your individual circumstances.

Could this protein discovery help prevent multiple sperm fertilising an egg during IVF?

The research showed that eggs shed their Juno protein within 40 minutes of fertilisation to prevent polyspermy (multiple sperm entering the egg), which would result in an unviable embryo. Understanding this mechanism better could help improve IVF techniques and embryo quality, which is regulated by the HFEA in the UK to ensure the highest standards of care.

Are there supplements that can help improve egg quality whilst TTC?

While no supplement can directly affect the Juno protein, maintaining good overall reproductive health is important when trying to conceive. Supplements containing Myo-Inositol, folic acid, and other essential vitamins may support healthy hormone balance and regular ovulation, complementing a balanced diet and lifestyle whilst you're TTC.