Simple sugars are key to complex sex.
It is common knowledge that fertilization in higher animals results from a fusing of egg and sperm. But only recently have scientists begun to describe the molecular mechanisms that govern the binding and interaction between these two unique cell types.
New research reported in Boston two weeks ago provides some of the finest details yet of the mechanics of fertilization, with potential implications for the fields of contraceptive technology and in vitro fertilization. Presented at the annual meeting of the American Association for the Advancement of Science, the research takes a bit of the mystery out of the miracle of conception, and suggests that fertilization may hinge on the mere presence or absence of a couple of hydrogen atoms on the human egg.
The study, led by Paul M. Wassarman of the Roche Institute of Molecular Biology in Nutley, N.J., focused on the insoluble outer coat, or zona pellucida, of the mammalian egg. Previous research had shown that the zona contains three varieties of glycoproteins (protein chains with carbohydrate branches), called ZP1, ZP2 and ZP3, and that ZP3 contains the specific receptor to which a sperm must bind to induce fertilization. But little was known about which part of the ZP3 molecule is critical to this binding, and even less was known about the "hardening" of the zona that follows within moments of fertilization. Zona hardening prevents subsequent sperm from also fertilizing the egg -- a phenomenon called polyspermy -- which would result in an overabundance of DNA in the developing egg and in most cases cell death.
Working with mouse eggs, which are very similar to human eggs, Wassarman focused on the so-called O-linked oligosaccharides, complex sugar chains that grow like branches off ZP3's protein "trunk." He induced minor changes in the branches to see which part of the oligosaccharide molecule actually binds to sperm. He reports that the six-carbon sugar alpha galactose -- a common sugar that, when bound to glucose, makes the milk sugar lactose -- appears to be the critical link to sperm recognition. Moreover, he found, if the No. 6 carbon on alpha galactose is oxidized to its aldehyde form, C-H = O, it fails to recognize sperm. In its reduced form, CH2-OH, the molecular complex binds to sperm, triggering a cascade of reactions that leads to the dissolving of cell membranes and the fusing of genetic material from the sperm and egg.
Although the simple loss of two hydrogens can thus make ZP3-bound galactose unrecognizable to sperm, Wassarman says that zona hardening following fertilization is probably a more complicated process than simply this. He hypothesizes that conformational changes in ZP3 chains following fertilization may activate specific enzymes to clip ZP2 chains into smaller pieces. Its structure thus disturbed, the molecular mesh surrounding the egg may collapse a bit, squeezing out water and making the zona impenetrate to late-arriving sperm.
It's possible, say Wassarman and others, that scientists may develop molecular biological techniques to induce zona hardening before fertilization, resulting in a very natural sort of contraception. Similarly, it may be possible to either produce antibodies against the sperm-binding oligosaccharides or mass-produce synthetic oligosaccharide to coat approaching sperm, thus blocking fertilization (SN: 7/21/84, p.38).
Alternatively, in the field of in vitro fertilization, a better understanding of zona hardening may make it easier to tell if a retrieved egg is still capable of being fertilized. Currently, scientists must look at retrieved eggs under a light microscope to determine an egg's viability and susceptibility to fertilization. That technique is less than perfect, however, and can result in expensive, futile attempts at fertilization.
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|Title Annotation:||research on mechanics of fertilization|
|Date:||Feb 27, 1988|
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