Sperm Receptors and Fertilization in Mammals

PAUL M. WASSARMAN, Ph. D.

Summary

All mammalian eggs share a common factor, they posses a thick extracellular coat
surrounding them, the zona pellucida, also known as ZP.

For fertilization to occur, sperm must bind and then penetrate the ZP, the term “species-
specific binding” means that the ZP will olny permit the entrance of sperm that comes from
the same specie. Furthermore, once a sperm gets into the egg, the ZP overcome some
changes that won’t allow any other sperm to enter, even though the next theory is yet to be
proven, “preliminary evidence suggests that inactivation can be atributed to enzymatic
destruction of essential mZP3 oligosaccharides.” (pg. 153)

This evidence supports the theory that the

ZP contains sperm-receptors that must be
recognized by sperm for them to bind to
unfertilized eggs in order to form a zygote.

The ZP is mouses is made up from three

different glycoproteins mZP1, mZP2 & mZP3.
A “zona domain” is constituted by 260
amino acids present in all ZP glycoproteins
present in all mammals, as well as in the C-
terminus of many other glycoproteins that
can be found through all the animalia
kingdom. mZP3 is the mouse sperm
receptor, “it consists of a polypeptide
backbone to which asparagine linked and
serine/threonine linked oligosaccharides
are covalently attached”, it is made up of
424 species of amino acids.

Incredibly, the ability of mZP3 to act as a sperm receptor doesn’t seem to be affected by high
temperatures, detergents, urants, reucing agents, or limited proteolysis, as weel as is not
dependent on the “extent of glycosylation of its polypeptide or on sulfurationand sialytation
of its oligosaccharides.” (pg. 151) From this observations, we are able to deduce that even
though mZP3 doesn’t play a direct role as sperm receptor function, it does in fact suggest
that “mZP3 oligosaccharides do play a role in sperm receptor function.” (pg. 151)

“Chemical and/or enzymatic removal of mZP 3 oligosaccharides results in a complete

inactivation of the protein as a sperm receptor.” (pg. 151) This information suggest that N-
acetylglucosamine, galactose and/or fucose are “essential sugars for sperm binding”, is a
result as well, that the essential olygosaccharides are just present in two of five serine
residues, serine-332 and serine-334, both of them located near the C-terminus of the
olygosaccharide. Interestingly, only this two serine residues are conserved from mouse to
human ZP3. Taking this into account, changes in compounds other tan –serine 332 & -serine
334, possibly in evolution may be the fact that alters the structure of O-linked
oligosaccharides, thereby “affect species specificity of sperm-egg interaction” (pg. 151)

Oogenesis and spermatogenesis prepare both, ovum and sperm, for fertilization. Sperm is
also capacited in the female reproductive tract, process that prepares the sperm to undergo
an Acrosome Reaction (AR). This can lead to the forming of a zygote or degeneration of the
cells.

“The acrosome is a large secretory vessicle that overlies the nucleus in the apical region of
the sperm head.” (pg. 151). As shown in the next figures.

Acrosome Reaction
There are two different membranes, “outer Acrosomal membrane”, which underlies
the plasma membrane, and “inner acrosomal membrane” that overlies the nucleus.
“Oly acrosomal reacted sperm (shown below) can peneé trate the ZP and fuse with the
egg plasma membrane.” (pg. 151).

Acrosome reacted sperm

Some molecules that participate in the secretion by somatic cells, also participate in
the iniciation of AR. This is triggered by the exposure of the sperm to mZP3.

Two different components may be essential for “intracelular membrane fusion in

somatic cells”: Rab3A GTPas & SNARE’s, which are present in mammalian sperm.

Recent studies suggest that IgG cross-linking of small mZP 3 glycopeptides bound to
sperm may induce the AR. Because of this observations, the “induction of the AR by
ZP3 probably will turno ut to be dependen ton multivalent interactions between ZP 3
and its binding-protein at the sperm surface.” (pg. 152).

“Furthermore, the absence of a ZP deleteriously affects oocyte growth, follicle-

development, and fertilization… The viscous border established by the ZP appears to
be necessary to stabilize interactions between the two cell types and promote
follicle development, incluiding oocyte growth.” (pg. 153).

Glossary

1. Acrosome reaction: the pattern of various chemical changes that occur in the
anterior of the head of the spermatozoon in response to contact with the
ovum and that lead to the sperm's penetration and fertilization of the ovum.
2. In vitro fertilization: medical procedure by which ovules and sperm are
combined in a laboratory.
3. Oligosaccharides: carbohydrates characterized by the simple sugars they
contain. This type of saccharide polymer contains between three and ten
simple sugars, also referred to as component sugars. These carbohydrates are
an important part of plasma membranes and play a role in the cell-cell
recognition within.