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CRM Blog: Fertility Journey

Binding “Mr. Right”: How Sperm Get into the Egg

August 18, 2014
By Dr. Randall Loy

How do swimming sperm cells and ovulated egg cells recognize each other and bind together? Despite substantial research, this question has been somewhat of a mystery for the past thirty plus years. The answer,  just in, may be a certain protein in the egg shell or zona pellucida.  The zona pellucida (Latin, “clear zone”) is the outer egg layer that surrounds and protects the egg as well as the embryo until it hatches out as a blastocyst (day 5-6 embryo). This soft, glassy layer binds sperm, allows one to enter and then blocks out all others. It appears that sperm bind to specific sugars associated with a particular zonal protein. In the human there are four zonal binding proteins, known as ZP1, ZP2, ZP3 and ZP4.

Sperm-egg binding abnormalities are especially seen among infertility patients and are thought to be a reason for unexplained infertility as well as failed ovulation induction and intrauterine insemination (IUI) cycles. In fact, approximately 8-10% of couples who have had three failed IUI cycles may have gamete binding abnormalities, especially if the semen count and/or percentage of normal forms are abnormal. Intracytoplasmic sperm injection (ICSI) has largely overcome this problem of binding abnormalities and should be a consideration in patients with unexplained infertility and multiple failed IUI cycles.

A recent study inThe Journal of Cell Biology(June 2014 DOI:10:1083/jcb.20140025) recently identified the protein in the zonal pellucida that sperm recognize and bind: ZP2. In this investigation, sperm did not bind the zona pellucida if it was missing ZP2. The researchers from the National Institute of Diabetes and Digestion and Kidney Diseases also found that sperm could not bind eggs if ZP2 was missing a critical region near the beginning of the protein. The entry one sperm through the zona causes the release of an enzyme that severs ZP2 in that critical region, thus preventing other sperm from entering. In the IVF setting we sometimes see a failure of this mechanism, especially in pre-mature or post-mature egg cells, and two or more sperm gain access to the egg nucleus.

The answer, then, to “How does one bind ‘Mr. Right?’” is ZP2!

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