Oocyte (or ovum/egg) activation is a series of processes that occur in the
oocyte
An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The femal ...
during
fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
.
Sperm entry causes calcium release into the oocyte. In mammals, this is caused by the introduction of
phospholipase C isoform zeta (PLCζ) from the sperm cytoplasm. Activation of the ovum includes the following events:
*
Cortical reaction
The cortical reaction is a process initiated during fertilization that prevents polyspermy, the fusion of multiple sperm with one egg. In contrast to the fast block of polyspermy which immediately but temporarily blocks additional sperm from fer ...
to block against other sperm cells
* Activation of egg metabolism
* Reactivation of meiosis
* DNA synthesis
Sperm trigger of egg activation
The sperm may trigger egg activation via the interaction between a sperm protein and an egg surface receptor.
Izumo is the sperm cell signal, that will trigger the egg receptor
Juno. This receptor is activated by the sperm binding and a possible signaling pathway could be the activation of a tyrosine kinase which then activates
phospholipase C (PLC). The inositol signaling system has been implicated as the pathway involved with egg activation. IP
3 and DAG are produced from the cleavage of PIP
2 by phospholipase C. However, another hypothesis is that a soluble 'sperm factor' diffuses from the sperm into the egg cytosol upon sperm-oocyte fusion. The results of this interaction could activate a
signal transduction pathway that uses
second messengers. A novel PLC isoform, PLCζ (
PLCZ1), may be the equivalent of the mammalian sperm factor. A 2002 study demonstrated that mammalian sperm contain PLC zeta which can start the signaling cascade.
Fast and slow block to polyspermy
Polyspermy
In biology, polyspermy describes the fertilization of an egg by more than one sperm. Diploid organisms normally contain two copies of each chromosome, one from each parent. The cell resulting from polyspermy, on the other hand, contains three or ...
is the condition when multiple sperm fuse with a single egg. This results in duplications of genetic material. In sea urchins, the block to polyspermy comes from two mechanisms: the
fast block and the
slow block. The fast block is an electrical block to polyspermy. The resting potential of an egg is -70mV. After contact with sperm, an influx of sodium ions increases the potential up to +20mV. The slow block is through a biochemical mechanism triggered by a wave of calcium increase. The rise of calcium is both necessary and sufficient to trigger the slow block. In the
cortical reaction
The cortical reaction is a process initiated during fertilization that prevents polyspermy, the fusion of multiple sperm with one egg. In contrast to the fast block of polyspermy which immediately but temporarily blocks additional sperm from fer ...
,
cortical granule
Cortical granules are regulatory secretory organelles (ranging from 0.2 um to 0.6 um in diameter) found within oocytes and are most associated with polyspermy prevention after the event of fertilization. Cortical granules are found among ...
s directly beneath the plasma membrane are released into the space between the plasma membrane and the
vitelline membrane
The vitelline membrane or vitelline envelope is a structure surrounding the outer surface of the plasma membrane of an ovum (the oolemma) or, in some animals (e.g., birds), the extracellular yolk and the oolemma. It is composed mostly of protein f ...
(the
perivitelline space
The perivitelline space is the space between the zona pellucida and the cell membrane of an oocyte or fertilized ovum. In the slow block to polyspermy, the cortical granules released from the ovum are deposited in the perivitelline space. Polysac ...
). An increase in calcium triggers this release. The contents of the granules contain
proteases
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...
,
mucopolysaccharides
Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...
,
hyalin, and
peroxidases
Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides.
Functionality
Peroxidases typically ca ...
. The proteases cleave the bridges connecting the plasma membrane and the vitelline membrane and cleave the bindin to release the sperm. The mucopolysaccharides attract water to raise the vitelline membrane. The hyalin forms a layer adjacent to the plasma membrane and the peroxidases cross-link the protein in the vitelline membrane to harden it and make it impenetrable to sperm. Through these molecules the vitelline membrane is transformed into the fertilization membrane or fertilization envelope. In mice, the zona reaction is the equivalent to the cortical reaction in sea urchins. The terminal sugars from ZP3 are cleaved to release the sperm and prevent new binding.
Reactivation of meiosis
The
meiotic cycle of the oocyte was suspended in metaphase of the second meiotic division. Once PLCζ is introduced into the oocyte by the sperm cell, it cleaves phospholipid phosphatidylinositol 4,5-bisphosphate (PIP
2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP
3). In most cells, this occurs at the cell membrane however, evidence suggests that the PIP
2 required for oocyte activation is potentially stored in intracellular vesicles dispersed throughout the cytoplasm. The IP
3 produced then triggers calcium oscillations which reactivate the meiotic cycle. This results in the production and extrusion of the second
polar body
A polar body is a small haploid cell that is formed at the same time as an egg cell during oogenesis, but generally does not have the ability to be fertilized. It is named from its polar position in the egg.
When certain diploid cells in animals ...
.
DNA synthesis
4 hours after fusion of sperm and ovum, DNA synthesis begins.
[ Male and female pronuclei move to the centre of the egg and membranes break down. Male ]protamines
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in t ...
are replaced with histones and the male DNA is demethylated. Chromosomes then orientate on the metaphase spindle for mitosis. This combination of the two genomes is called syngamy.[
The sperm contributes a ]pronucleus
A pronucleus () is the nucleus of a sperm or egg cell during the process of fertilization. The sperm cell becomes a pronucleus after the sperm enters the ovum, but before the genetic material of the sperm and egg fuse. Contrary to the sperm cell, ...
and a centriole to the egg. Most other components and organelles are rapidly degraded. Mitochondria are rapidly ubiquinated and destroyed. Oxidative stress theory is a hypothesis that it is evolutionarily favourable for mitochondria from the father to be destroyed, as it there is a greater possibility that the mitochondrial DNA has become mutated or damaged. This is because mtDNA is not protected by histones and has poor repair mechanisms. Due to the increased metabolic activity of the sperm compared to the egg, due to its motility, there is greater production of reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
and therefore greater chance of mutation.[ Furthermore, sperm are exposed to reactive oxygen species from leukocytes in the epididymis during transit.][ Additionally, quality control of spermatozoa is much worse than for the ovum, as many sperm are released whereas only one dominant follicle is released per cycle. This competitive selection helps to ensure the most 'fit' ova are selected for fertilisation.][
]
Artificial oocyte activation
Oocyte activation may be artificially facilitated by calcium ionophore
In chemistry, an ionophore () is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as liq ...
s, something that is speculated to be useful in case of fertilization failure, such as still occurs in 1–5% of intracytoplasmic sperm injection
Intracytoplasmic sperm injection (ICSI ) is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of em ...
(ICSI) cycles. Another of method is by using the drug Roscovitine, this reduces the activity of M-phase promoting factor activity in mice.
Indications for artificial oocyte activation include:
*Oocyte related activation deficiency
* In vitro maturation
*Low number of oocytes at retrieval
*Severe teratozoospermia
Teratospermia or teratozoospermia is a condition characterized by the presence of sperm with abnormal morphology that affects fertility in males.
Causes
The causes of teratozoospermia are unknown in most cases. However, Hodgkin's disease, coelia ...
*Severe oligoasthenoteratozoospermia
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen, ...
*Globozoospermia
Globozoospermia is a rare and severe form of monomorphic teratozoospermia. This means that the spermatozoa show the same abnormality, and over 85% of spermatozoa in sperm have this abnormality. Globozoospermia is responsible for less than 0.1% of m ...
*Testicular sperm extraction ( MicroTESE)
*Previous fertilization failure
*Unexplained infertility
Unexplained infertility is infertility that is idiopathic in the sense that its cause remains unknown even after an infertility work-up, usually including semen analysis in the man and assessment of ovulation and fallopian tubes in the woman.merck ...
*Frozen-thawed oocytes
References
{{embryology
Embryology