Hyperactivation of sperm

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What is hyperactivation of sperm and why is it important? Referring to experimental evidence, explain how hyperactivation is thought to be controlled.


Reproduction is an important process that leads to the production of offspring and is essential in passing a particular organism's genes onto the next generation. Sexual reproduction involves combining the genomes of two different individuals in order to produce offspring that are genetically different from both of the parents.This depends on the fusion of two haploid gametes one from each parent, this process is known as fertilisation. In most animals the gametes are an egg cell or oocyte from the female and a sperm cell or spermatozoon from the male, these specialised cells become haploid via a process called meiosis. Meiosis is also important as it creates genetic diversity via independent assortment and recombination or 'crossing-over' of homologous chromosomes.1

Oocytes or egg cells are produced in the ovaries of females and their formation and development occurs in a variety of controlled steps. In most vertebrates the formation of an egg cell begins when primordial germ cells (PGC's) migrate to the gonad during the early stages of embryogenesis and is not completed until fertilisation from a sperm cell has occurred. An oocyte has various specialised structures these include a nucleus that contains haploid DNA, an extra cellular matrix that surrounds and protects the egg cell called the zona pellucida and specialised secretory vesicles called cortical granules that are involved in preventing polyspermy.

Spermatozoa are highly specialised gametes that are produced in the testes of the male through a process called spermatogenesis. Unlike egg cells sperm are produced in males on the onset of puberty. provides a diagrammatic representation of the structure of a human sperm cell. The cell is crudely split into two main parts, the head region and tail region. The tail of the sperm includes the flagellum and the midpiece, the flagellum is an important structure because it is involved in the motility of the sperm cell through the female reproductive tract. The midpiece contains the mitochondria that are required to produce the ATP that is essential to maintain the motility of the sperm cell. The head of the sperm contains the haploid nucleus and the acrosome vesicle which contains hydrolytic enzymes that are released in the acrosome reaction.

Motility in Spermatozoa

Spermatozoa are highly motile cells and this is an essential characteristic as they need to navigate and move through the female reproductive tract in order to locate the egg cell for fertilisation. Any dysfunctions in motility can lead to male related infertility as the sperm cells are unable to locate the oocyte in the female reproductive tract, highlighting the importance of correct motility. Problems in sperm motility lead to a condition in males called asthenozoospermia; this generally causes infertility in males.

Therefore, normal motility needs to be observed in sperm cells in order for them to be of good quality. One type of normal movement pattern observed in sperm cells is known as activated motility. This occurs when the sperm cells are released from their stores in the epididymis of the male reproductive tract along with seminal fluids. Activated movement involves the sperm cells swimming vigorously in a straight line trajectory while the beating of the flagellum is symmetrical.

The other form of motility observed in sperm is a movement pattern called hyperactivation. The following essay will discuss in detail what hyperactivation is, how it is controlled and the importance of it in the fertilisation process of sexual reproduction.


The distinctive movement patterns of spermatozoa, now recognised as hyperactivation, were first observed by Yanagimachi in 1969 when it was noticed that hamster spermatozoa underwent a distinct change in motility around the same time of fertilisation. Hyperactivation is generally characterised by an increase in flagellar bend and an increase in beat amplitude. shows the distinct difference in patterns of motility that can be observed from activated and hyperactivated sperm cells.

Hyperactivation is now recognised as an important pattern in motility that needs to occur in order for sperm to successfully fertilise the oocyte. There are various studies that have highlighted the benefits of hyperactivated movement for sperm cells that are travelling through the female reproductive tract.

Firstly, it has been identified that the environment that sperm cells encounter in the female reproductive tract is very viscous as thick mucous secretions are present in the oviduct. Various studies have proved that hyperactivated sperm are equipped to move through this extremely viscous environment due to their vigorous beating patterns. One study in particular, by Suarez and Dai in 1992, recreated the viscoelastic environment of the oviduct in vitro by using methylcellulose and long chain polyacrylamide. This study discovered that hyperactivated mouse sperm were more efficient at penetrating and moving through this viscoelastic media compared to non-hyperactivated sperm. Therefore, this proves that hyperactivated motility would help the sperm navigate through the mucous environment of the oviduct.

Furthermore, there is evidence that shows that the process of hyperactivation plays a critical role in aiding the sperm cell to penetrate the zona pellucida of the egg cell. This process is essential in order for fertilisation to take place as the extracellular matrix of the zona pellucida acts as a physical barrier to the sperm cells. A study done by Stauss et al in 1995 showed that hyperactivated hamster spermatozoa were able to penetrate the zona pellucida of the egg cell successfully due to their vigorous beating pattern. However, when hyperactivation was prevented, by blocking Ca2+channels, the sperm cells were unable to penetrate the extra cellular matrix of the zona pellucida. Therefore, this study proves that hyperactivation is required for the spermatozoa to be able to penetrate the zona pellucida in order to fertilise the oocyte.

Another reason why hyperactivated movement is advantageous to sperm was discovered in a study by Suarez and Osman in 1987. Whilst observing the patterns of movement of mice spermatozoa in the oviduct they discovered that the sperm cells that were hyperactivated were more efficient at searching for and locating the oocyte. This is because the more pronounced flagellar beat associated with hyperactivation allows the sperm cells to enter and leave the folds of the oviduct walls more easily and with more efficiency. In addition to this, Pacey et al in 1995 observed that hyperactivated human sperm were able to detach from the epithelium of the oviduct more effectively than non-hyperactivated sperm. Therefore, hyperactivated motility is advantageous for spermatozoa when they travel through the female reproductive tract trying to locate the oocyte to fertilise.

The Trigger for Hyperactivation

It is not known what exact factors induce hyperactivation of spermatozoa in vivo at the correct time and place. However, as hyperactivation of sperm cells occurs when they are inside the female reproductive tract it is widely considered that various signals from the female reproductive tract induce hyperactivation.

There is evidence that suggests that follicular fluid, which is released during ovulation, triggers hyperactivated movement patterns in spermatozoa. It has already been determined that follicular fluid exhibits a chemotactic effect because it attracts spermatozoa to the site where the oocyte is located. A study by Yao et al in 2000 discovered that human spermatozoa that were treated with human follicular fluid showed increased hyperactivated motility compared to sperm cells that were not treated with human follicular fluid. Furthermore, this study determined that increased doses of follicular fluid increased hyperactivation in the sperm cells.

In order for follicular fluid to effect spermatozoa motility ovulation has to occur because that is when the fluid is released into the oviduct. However, hyperactivated sperm have been observed in the female genital tract before ovulation has occurred which suggests that another factor induces hyperactivation. Therefore, there is conflicting evidence as to whether follicular fluid is the factor that induces hyperactivated motility in spermatozoa.

Control of Hyperactivation

There are various studies that have proven that Ca2+ is an extremely important signalling molecule within sperm and that it is essential in inducing hyperactivated motility. A study by Suarez et al in 1987 showed that hyperactivated movement patterns were exhibited in sperm cells that were treated with a Ca2+ ionophore. An additional study, by Suarez et al in 1993, showed that Ca2+ levels in the flagella of hamster sperm cells were higher in the hyperactivated sperm compared to activated sperm.

Furthermore, an important study done by Ho et al in 2002 showed that Ca2+ acts directly on the cytoskeletal elements of spermatozoa in order to induce hyperactivated motility. The study involved demembranating bull sperm using triton X-100; this left the cytoskeletal components of the sperm cells exposed. Then the demembranted sperm cells were placed in mediums containing varying concentrations of Ca2+. At a Ca2+ concentration of 100 nM some of the sperm cells began to exhibit hyperactivated motility and at a concentration of 400 nM most sperm cells underwent hyperactivation. Therefore, this study shows that Ca2+ is an essential signalling molecule for inducing hyperactivated motility in sperm cells and that the Ca2+ acts on cytoskeletal constituents such as the axoneme.

All the above mentioned studies establish that Ca2+ is essential in the induction of hyperactivated motility in sperm cells, it is now important to determine where the Ca2+ comes from in order to act on the axoneme to induce this specialised motility pattern. Ca2+ can either come from the extra cellular environment or from intracellular Ca2+ stores located within the sperm cell.

Firstly, if sperm cells were to obtain extracellular Ca2+ they would require specialised Ca2+ plasma membrane channels. One such channel has been discovered to be located on the flagellum of spermatozoa and this Ca2+ channel is called CatSper. There are four human CatSper proteins and it was discovered by Ren et al in 2001 that they are all required for male fertility. This is because if male mice had a knockout of any one CatSper gene their sperm failed to hyperactivate and they were infertile. Therefore, all four CatSper proteins play important roles in inducing hyperactivation of sperm cells.

The importance of CatSper channels on motility of sperm and fertility of males have been documented in various studies. Firstly, a study by Nikpoor et al in 2004 showed that levels of CatSper proteins were low in a group of males that had defects in sperm motility and fertility. Furthermore, another study by Quill et al in 2003 showed that spermatozoa from CatSper null mutant mice were unable to undergo hyperactivated motility and they were also unable to penetrate the zona pellucida of the oocyte.

An extremely important study on the importance of CatSper proteins in humans was done by Avidan et al in 2003. This study describes three brothers that all suffer from Congenital Dyserythropoietic Anemia Type I (CDA1) which is caused by mutations of the CDAN1 gene located on chromosome 15. These mutations led to the deletion of the gene encoding the CatSper2 protein and it was observed that all three brothers were infertile and their sperm cells exhibited abnormal morphology and motility. Therefore, all the above studies prove that CatSper proteins are essential in inducing hyperactivation and are subsequently essential for the fertilising ability of the sperm cells.

There is evidence that Ca2+ required for the hyperactivated movement patterns in spermatozoa can be obtained from intracellular stores. A study done by Ho and Suarez in 2001 showed that bull spermatozoa underwent hyperactivated motility despite not being in a medium containing extracellular Ca2+. Furthermore, another study by Ho and Suarez in 2003 determined that a possible site for these intracellular stores could be the redundant nuclear envelope (RNE) which is located at the top of the flagellum.

Along with Ca2+ there are other factors that have been proven to play a role in controlling hyperactivated motility in sperm cells. Firstly, it was shown by Kirichok et al in 2006 that CatSper proteins are regulated by pH; an increase in pH will open up the CatSper channels in vitro allowing extracellular Ca2+ to enter the sperm cell. This is important as sperm cells encounter a slight increase in pH as they navigate through the female reproductive tract. Furthermore, a study by Chan et al in 1998 showed that increases in tyrosine phosphorylation can control heat induced hyperactivated motility in human spermatozoa.


In conclusion, hyperactivation is an extremely important movement pattern observed in spermatozoa when they are in the female reproductive tract. This type of motility is essential for the sperm cells ability to navigate through the mucous environment of the female reproductive tract, to efficiently locate the oocyte and then to penetrate the cumulus cells and the zona pellucida in order to fertilise the oocyte. It is important to note that another event occurs in a sperm cell that is essential in order for it to be able to fertilise the oocyte, this event is known as capacitation. This process prepares the sperm cell to undergo the acrosome reaction and it is induced by increased levels of Ca2+ that then lead to increases in intracellular cAMP. Although capacitation and hyperactivation can occur around the same time in spermatozoa they are two separate processes controlled by separate pathways.2

Although, an exact in vivo signal for inducing hyperactivation is yet to be determined, hyperactivation is mainly controlled by the important signalling molecule Ca2+ which can either come from the extra cellular environment via calcium channels such as CatSper or from intracellular stores such as the redundant nuclear envelope. However, there are other factors that are involved in controlling hyperactivation such as increases in pH and increases in tyrosine phosphorylation. Overall, hyperactivation in sperm cells is an important event and is required for successful fertilisation to take place. Problems in hyperactivated motility in spermatozoa can lead to male related infertility.