Acrosome reaction

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Acrosome reaction on a Sea Urchin cell Acrosome reaction diagram en.svg
Acrosome reaction on a Sea Urchin cell

For fertilization to happen between a sperm and egg cell, a sperm must first fuse with the plasma membrane and then penetrate the female egg cell to fertilize it. While the fusion of the sperm cell with the egg cell's plasma membrane is relatively straightforward, penetrating the egg's protective layers, such as the zona pellucida, presents a significant challenge. Therefore, sperm cells go through a process known as the acrosome reaction, which is the reaction that occurs in the acrosome of the sperm as it approaches the egg.

Contents

The acrosome is a membrane-bound organelle of Golgi apparatus origin, commonly located at the tip of the head of the mature spermatozoon, Which contains a variety of enzymes and antigens required for fertilization. It was once called "apical body" because of its location, or "perforatorium" on the assumption that it might assist the spermatozoon boring into the egg. [1]

Acrosomal Reaction Acrosomal Reaction.svg
Acrosomal Reaction

As the sperm approaches the zona pellucida of the egg, which is necessary for initiating the acrosome reaction, the membrane surrounding the acrosome fuses with the plasma membrane of the sperm's head, exposing the contents of the acrosome. The contents include surface antigens necessary for binding to the egg's cell membrane, and numerous enzymes which are responsible for breaking through the egg's tough coating and allowing fertilization to occur. [2]

Variations among species

There are considerable species variations in the morphology and consequences of the acrosome reaction. In several species, the trigger for the acrosome reaction has been identified in a layer that surrounds the egg.

Echinoderms

In some lower animal species, a protuberance (the acrosomal process) forms at the apex of the sperm head, supported by a core of actin microfilaments. The membrane at the tip of the acrosomal process fuses with the egg's plasma membrane.

In some echinoderms, including starfish and sea urchins, a significant portion of the exposed acrosomal content contains a protein that temporarily holds the sperm on the egg's surface.

Mammals

In mammals, the acrosome reaction releases hyaluronidase and acrosin; their role in fertilization is not yet clear. The acrosomal reaction is initiated when sperm comes into contact with the oocyte's zona pellucida. Upon coming into contact with the zona pellucida, the acrosomal enzymes begin to dissolve, and the actin filament comes into contact with the zona pellucida. Once the two meet, a calcium influx occurs, causing a signaling cascade. The cortical granules inside the oocyte then fuse to the outer membrane, and a quick fast block reaction occurs.

Furthermore, the cortical granules inside the oocyte fuse with the outer membrane, initiating a rapid block reaction. This reaction alters a patch of pre-existing sperm plasma membrane, facilitating fusion with the egg plasma membrane.

A sperm penetration assay includes an acrosome reaction test that assesses how well a sperm can perform during the fertilization process. Sperm that are unable to go through the acrosome reaction properly will not be able to fertilize an egg. However, this problem only occurs in about 5% of men that have the test done. This test is rather expensive and provides limited information on a man's fertility. [3]

In other cases, such as in the wood mouse Apodemus sylvaticus, premature acrosome reactions have been found to cause increased motility in aggregates of spermatozoa promoting fertilization. [4]

The process

The acrosomal reaction typically occurs in the ampulla of the fallopian tube, the site of fertilization, when the sperm penetrates the secondary oocyte. Prior events prepare for the acrosome reaction. The sperm cell undergoes a series of changes, including acquiring a "hyperactive motility pattern" where its flagellum produces vigorous whip-like movements propelling the sperm through the cervical canal and uterine cavity until it reaches the isthmus of the fallopian tube. Various mechanisms, including chemotaxis, aid the sperm in approaching the ovum in the ampulla of the fallopian tube. Once in close proximity, glycoproteins on the outer surface of the sperm bind with glycoproteins on the zona pellucida of the ovum.

Sperm that fail to initiate the acrosome reaction prior to reaching to the zona pellucida are unable to penetrate the zona pellucida. Since the acrosome reaction has already occurred, sperm are then able to penetrate the zona pellucida due to mechanical action of the tail, not because of the acrosome reaction itself. [5]

The first stage is the penetration of corona radiata, by releasing hyaluronidase from the acrosome to digest cumulus cells surrounding the oocyte and exposing acrosin attached to the inner membrane of the sperm. The cumulus cells are embedded in a gel-like substance made primarily of hyaluronic acid, and developed in the ovary with the egg and support it as it grows. The acrosome reaction must occur before the sperm cell reaches the zona pellucida. [5]

Acrosin, once exposed, digests the zona pellucida and membrane of the oocyte, allowing for penetration to happen. Part of the sperm's cell membrane then fuses with the egg cell's membrane, and the contents of the head sink into the egg. In the mouse, it has been demonstrated that ZP3, one of the proteins that make up the zona pellucida, binds to a partner molecule (to the β1,4-galactosyl transferase receptors) on the sperm. This lock-and-key type mechanism is species-specific and prevents the sperm and egg of different species from fusing. The zona pellucida also releases Ca granules to prevent other sperm from binding. There is some evidence that this binding is what triggers the acrosome to release the enzymes that allow the sperm to fuse with the egg. A similar mechanism likely occurs in other mammals, but the diversity of zona proteins across species means that the relevant protein and receptor may differ.

More recent scientific evidence demonstrates that the acrosomal reaction is necessary to expose a protein called IZUMO1 on the sperm: without the reaction, sperm can still penetrate through the zona pellucida to the egg membrane, but cannot fuse. [6] As seen in mouse studies, IZUMO1 binds to the oocyte protein JUNO and once bound together, the sperm and the egg fuse together to form two pronuclei. [7] [8] These pronuclei supply the zygote with the genetic material necessary for the formation of an embryo. Additionally, once the fusion of the sperm and oocyte is complete, phospholipase C zeta is released from the sperm.

Following penetration and fusion, if all is normally occurring, the process of egg-activation occurs facilitated by proteins like phospholipase C zeta, and the oocyte is said to have become activated. This is thought to be induced by a specific protein phospholipase c zeta. It undergoes its secondary meiotic division, and the two haploid nuclei (paternal and maternal) fuse to form a zygote. To prevent polyspermy and minimize the possibility of producing a triploid zygote, several changes to the egg's cell membranes render them impenetrable shortly after the first sperm enters the egg (such as the rapid loss of JUNO). [8]

Spontaneous acrosome reaction

Spermatozoa can initiate the acrosomal reaction well in advance of reaching the zona pellucida, as well as in vitro in an appropriate culture medium. This is referred to as spontaneous acrosome reaction (SAR).

It is now known that in a certain sense, this phenomenon is physiologically normal across mammalian species. The acrosome reaction is induced by passage through the cumulus oophorus cells, mediated by the hormones they secrete (such as progesterone, LPA, LPC). [6] [9] [10]

However, the physiological role of truly spontaneous acrosomal reaction, occurring well before this point in the female reproductive tract, or in vitro, is a separate phenomenon.

In mice, it has been well established as physiologically normal and common. Mouse sperm which have undergone fully spontaneous acrosome reaction are still able to fertilize eggs. [6] Furthermore, the rate of spontaneous acrosome reaction is higher in more promiscuous species such as Apodemus sylvaticus , which face a high level of sperm competition. [11]

In humans, on the other hand, it remains disputed where exactly the acrosome reaction is initiated in physiological fertilization, due to experimental constraints (for example, animal studies may make use of transgenic mice with fluorescent sperm, while human studies cannot). [10]

Studies have been done with the intent of linking in vitro SAR rate in human sperm to sperm quality and fertilization rate, but the overall results are mixed, and do not seem to be clinically useful as of 2018. [12]

In in vitro fertilization

When using intracytoplasmic sperm injection (ICSI) for IVF, the implantation rate is higher in oocytes injected with spermatozoa that have undergone acrosome reaction (~40%) vs. those injected with nonreacted spermatozoa (~10%). The implantation rate is ~25% in when injected with both reacted and nonreacted spermatozoa. The delivery rate per cycle follows the same trend. [13]

The acrosome reaction can be stimulated in vitro by substances a sperm cell may encounter naturally, such as progesterone or follicular fluid, as well as the more commonly used calcium ionophore A23187.

Assessment

Birefringence microscopy, [13] flow cytometry [14] or fluorescence microscopy can be used for assessing the shedding of the acrosome or "acrosome reaction" of a sperm sample. Flow cytometry and fluorescence microscopy are usually done after staining with a fluoresceinated lectin such as FITC-PNA, FITC-PSA, FITC-ConA, or fluoresceinated antibody such as FITC-CD46. [15] The antibodies/lectins have a high specificity for different parts of the acrosomal region, and will only bind to a specific site (acrosomal content/ inner/outer membrane). If bound to a fluorescent molecule, regions where these probes have bound can be visualised. Sperm cells with artificially induced acrosome reactions may serve as positive controls.

For fluorescence microscopy, a smear of washed sperm cells is made, air-dried, permeabilized, and then stained. Such a slide is then viewed under the light of a wavelength that will cause the probe to fluoresce if it is bound to the acrosomal region. At least 200 cells are considered arbitrarily and classified as either acrosome intact (fluorescing bright green), or acrosome reacted (no probe present, or only on the equatorial region). It is then expressed as a percentage of the counted cells.

For assessment with flow cytometry, the washed cells are incubated with the chosen probe, possibly passed again, then sampled in a flow cytometer. After gating the cell population according to forward- and side-scatter, the resulting data can be analyzed (E.g. mean fluorescences compared). With this technique, a probe for viability such as propidium iodide (PI) could also be included in order to exclude dead cells from the acrosome assessment, since many sperm cells will spontaneously lose their acrosome when they die.

See also

Related Research Articles

<span class="mw-page-title-main">Spermatozoon</span> Motile sperm cell

A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote.

<span class="mw-page-title-main">Fertilisation</span> Union of gametes of opposite sexes during the process of sexual reproduction to form a zygote

Fertilisation or fertilization, also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a zygote and initiate its development into a new individual organism or offspring. While processes such as insemination or pollination, which happen before the fusion of gametes, are also sometimes informally referred to as fertilisation, these are technically separate processes. The cycle of fertilisation and development of new individuals is called sexual reproduction. During double fertilisation in angiosperms, the haploid male gamete combines with two haploid polar nuclei to form a triploid primary endosperm nucleus by the process of vegetative fertilisation.

<span class="mw-page-title-main">Acrosome</span> Organelle of sperm cells

The acrosome is an organelle that develops over the anterior (front) half of the head in the spermatozoa of humans, and many other animals. It is a cap-like structure derived from the Golgi apparatus. In placental mammals, the acrosome contains degradative enzymes. These enzymes break down the outer membrane of the ovum, called the zona pellucida, allowing the haploid nucleus in the sperm cell to join with the haploid nucleus in the ovum. This shedding of the acrosome, or acrosome reaction, can be stimulated in vitro by substances a sperm cell may encounter naturally such as progesterone or follicular fluid, as well as the more commonly used calcium ionophore A23187. This can be done to serve as a positive control when assessing the acrosome reaction of a sperm sample by flow cytometry or fluorescence microscopy. This is usually done after staining with a fluoresceinated lectin such as FITC-PNA, FITC-PSA, FITC-ConA, or fluoresceinated antibody such as FITC-CD46.

<span class="mw-page-title-main">Zona pellucida</span> Glycoprotein layer surrounding the plasma membrane of mammalian oocytes

The zona pellucida is the specialized area surrounding mammalian oocytes (eggs). It is also known as an egg coat. The zona pellucida is essential for oocyte growth and fertilization.

Capacitation is the penultimate step in the maturation of mammalian spermatozoa and is required to render them competent to fertilize an oocyte. This step is a biochemical event; the sperm move normally and look mature prior to capacitation. In vivo, capacitation occurs after ejaculation, when the spermatozoa leave the vagina and enter the upper female reproductive tract. The uterus aids in the steps of capacitation by secreting sterol-binding albumin, lipoproteins, and proteolytic and glycosidasic enzymes such as heparin.

Hyperactivation is a type of sperm motility. Hyperactivated sperm motility is characterised by a high amplitude, asymmetrical beating pattern of the sperm tail (flagellum). This type of motility may aid in sperm penetration of the zona pellucida, which encloses the ovum.

<span class="mw-page-title-main">Acrosin</span> Mammalian protein found in Homo sapiens

Acrosin is a digestive enzyme that acts as a protease. In humans, acrosin is encoded by the ACR gene. Acrosin is released from the acrosome of spermatozoa as a consequence of the acrosome reaction. It aids in the penetration of the Zona Pellucida.

<span class="mw-page-title-main">Human fertilization</span> Union of a human egg and sperm

Human fertilization is the union of an egg and sperm, occurring primarily in the ampulla of the fallopian tube. The result of this union leads to the production of a fertilized egg called a zygote, initiating embryonic development. Scientists discovered the dynamics of human fertilization in the 19th century.

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 more copies of each chromosome—one from the egg and one each from multiple sperm. Usually, the result is an unviable zygote. This may occur because sperm are too efficient at reaching and fertilizing eggs due to the selective pressures of sperm competition. Such a situation is often deleterious to the female: in other words, the male–male competition among sperm spills over to create sexual conflict.

<span class="mw-page-title-main">Cortical reaction</span> Biological process that prevents polyspermy

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 fertilizing the egg, the cortical reaction gradually establishes a permanent barrier to sperm entry and functions as the main part of the slow block of polyspermy in many animals.

Decapacitation factor (DF) is composed of sperm surface-associated proteins which modulate the fertilizing ability of spermatozoa. Decapacitation is a reversible process that converts fertile, capacitated sperm to less-fertile uncapacitated sperm. This activity is achieved by interaction between cholesterol, phospholipids and fibronectin-like substances and delivered via small vesicles in seminal plasma. DF prevents onset of capacitation. Many DFs are released in secretions from the epididymis and accessory organs of the male reproductive system. However, some DFs have been identified that are located on the acrosome of sperm. Normally, capacitation is initiated through the loss of DF before the spermatozoa can perform the acrosomal reaction. Physiologically decapacitation will inhibit the acrosomal reaction as DFs reassociate onto the sperm surface. For example, one way this can be achieved is through spermatozoal membrane stabilization by maintaining physiological cholesterol/phospholipid ratio.

The vitelline membrane or vitelline envelope is a structure surrounding the outer surface of the plasma membrane of an ovum or, in some animals, the extracellular yolk and the oolemma. It is composed mostly of protein fibers, with protein receptors needed for sperm binding which, in turn, are bound to sperm plasma membrane receptors. The species-specificity between these receptors contributes to prevention of breeding between different species. It is called zona pellucida in mammals. Between the vitelline membrane and zona pellucida is a fluid-filled perivitelline space.

<span class="mw-page-title-main">ZP3</span> Protein-coding gene in the species Homo sapiens

Zona pellucida sperm-binding protein 3, also known as zona pellucida glycoprotein 3 (Zp-3) or the sperm receptor, is a ZP module-containing protein that in humans is encoded by the ZP3 gene. ZP3 is the glycoprotein in the zona pellucida most important for inducting the acrosome reaction of sperm cells at the beginning of fertilization.

<span class="mw-page-title-main">ZP2</span> Protein-coding gene in the species Homo sapiens

Zona pellucida sperm-binding protein 2 is a protein that in humans is encoded by the ZP2 gene.

<span class="mw-page-title-main">ZP4</span> Protein-coding gene in the species Homo sapiens

Zona pellucida sperm-binding protein 4, ZP-4 or avilesine, named after its discoverer Manuel Avilés Sánchez is a protein that in humans is encoded by the ZP4 gene.

Oocyteactivation is a series of processes that occur in the oocyte during fertilization.

<span class="mw-page-title-main">Cortical granule</span>

Cortical granules are regulatory secretory organelles found within oocytes and are most associated with polyspermy prevention after the event of fertilization. Cortical granules are found among all mammals, many vertebrates, and some invertebrates. Within the oocyte, cortical granules are located along the cortex, the region furthest from the cell's center. Following fertilization, a signaling pathway induces the cortical granules to fuse with the oocyte's cell membrane and release their contents into the oocyte's extracellular matrix. This exocytosis of cortical granules is known as the cortical reaction. In mammals, the oocyte's extracellular matrix includes a surrounding layer of perivitelline space, zona pellucida, and finally cumulus cells. Experimental evidence has demonstrated that the released contents of the cortical granules modify the oocyte's extracellular matrix, particularly the zona pellucida. This alteration of the zona pellucida components is known as the zona reaction. The cortical reaction does not occur in all mammals, suggesting the likelihood of other functional purposes for cortical granules. In addition to modifying the oocyte's extracellular matrix and establishing a block to polyspermy, the exocytosis of cortical granules may also contribute towards protection and support of the developing embryo during preimplantation. Once the cortical granules complete their functions, the oocyte does not replenish them.

<span class="mw-page-title-main">IZUMO1</span> Protein-coding gene in the species Homo sapiens

Izumo sperm-egg fusion protein 1 is encoded in humans by the IZUMO1 gene. In mammalian fertilisation, IZUMO1 binds to its egg receptor counterpart, Juno, to facilitate recognition and fusion of the gametes.

<span class="mw-page-title-main">Globozoospermia</span> Medical condition

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 male infertility. It is characterised by round-headed spermatozoa without acrosomes, an abnormal nuclear membrane and midpiece defects. Affected males therefore suffer from either reduced fertility or infertility. Studies suggest that globozoospermia can be either total or partial, however it is unclear whether these two forms are variations on the same syndrome, or actually different syndromes.

Paul Michael Wassarman is an American biologist who has been Professor in the Dept. of Cell, Developmental, and Regenerative Biology at the Icahn School of Medicine at Mount Sinai since 1996. His laboratory identified and characterised proteins that make up the zona pellucida (ZP) of mammalian eggs and determined their role in fertilisation.

References

  1. ↑ Hirohashi, Noritaka; Yanagimachi, Ryuzo (2018-07-01). "Sperm acrosome reaction: its site and role in fertilization". Biology of Reproduction. 99 (1): 127–133. doi: 10.1093/biolre/ioy045 . ISSN   1529-7268. PMID   29462288.
  2. ↑ Swiss Virtual Campus. "Chapter 4, Fertilization". Human Embryology. universities of Fribourg, Lausanne and Bern. Archived from the original on 18 February 2019. Retrieved 18 February 2017.
  3. ↑ "Your path to fertility: Acrosome Reaction". 2007.[ unreliable medical source? ]
  4. ↑ Moore, Harry; Dvoráková, Katerina; Jenkins, Nicholas; Breed, William (2002). "Exceptional sperm cooperation in the wood mouse" (PDF). Nature. 418 (6894): 174–7. doi:10.1038/nature00832. PMID   12110888. S2CID   4413444.
  5. 1 2 Inoue, N; Satouh, Y; Ikawa, M; Okabe, M; Yanagimachi, R (2011). "Acrosome-reacted mouse spermatozoa recovered from the perivitelline space can fertilize other eggs". Proceedings of the National Academy of Sciences. 108 (50): 20008–11. Bibcode:2011PNAS..10820008I. doi: 10.1073/pnas.1116965108 . PMC   3250175 . PMID   22084105.
  6. 1 2 3 Ikawa, Masahito; Inoue, Naokazu; Benham, Adam M.; Okabe, Masaru (2010-04-01). "Fertilization: a sperm's journey to and interaction with the oocyte". The Journal of Clinical Investigation. 120 (4): 984–994. doi:10.1172/JCI41585. ISSN   0021-9738. PMC   2846064 . PMID   20364096.
  7. ↑ Inoue, Naokazu; Satouh, Yuhkoh; Ikawa, Masahito; Okabe, Masaru; Yanagimachi, Ryuzo (2011-12-13). "Acrosome-reacted mouse spermatozoa recovered from the perivitelline space can fertilize other eggs". Proceedings of the National Academy of Sciences of the United States of America. 108 (50): 20008–20011. doi: 10.1073/pnas.1116965108 . ISSN   0027-8424. PMC   3250175 . PMID   22084105.
  8. 1 2 Bianchi, Enrica; Doe, Brendan; Goulding, David; Wright, Gavin J. (2014-04-24). "Juno is the egg Izumo receptor and is essential for mammalian fertilisation". Nature. 508 (7497): 483–487. Bibcode:2014Natur.508..483B. doi:10.1038/nature13203. ISSN   0028-0836. PMC   3998876 . PMID   24739963.
  9. ↑ Bosakova, Tereza; Tockstein, Antonin; Sebkova, Natasa; Simonik, Ondrej; Adamusova, Hana; Albrechtova, Jana; Albrecht, Tomas; Bosakova, Zuzana; Dvorakova-Hortova, Katerina (2018-12-12). "New Insight into Sperm Capacitation: A Novel Mechanism of 17β-Estradiol Signalling". International Journal of Molecular Sciences. 19 (12): 4011. doi: 10.3390/ijms19124011 . ISSN   1422-0067. PMC   6321110 . PMID   30545117.
  10. 1 2 Gómez-Torres, María José; García, Eva María; Guerrero, Jaime; Medina, Sonia; Izquierdo-Rico, María José; Gil-Izquierdo, Ángel; Orduna, Jesús; Savirón, María; González-Brusi, Leopoldo; Ten, Jorge; Bernabeu, Rafael (2015-11-09). "Metabolites involved in cellular communication among human cumulus-oocyte-complex and sperm during in vitro fertilization". Reproductive Biology and Endocrinology. 13: 123. doi: 10.1186/s12958-015-0118-9 . ISSN   1477-7827. PMC   4640411 . PMID   26553294.
  11. ↑ Sebkova, Natasa; Ded, Lukas; Vesela, Katerina; Dvorakova-Hortova, Katerina (2014-02-01). "Progress of sperm IZUMO1 relocation during spontaneous acrosome reaction". Reproduction. 147 (2): 231–240. doi: 10.1530/REP-13-0193 . ISSN   1741-7899. PMID   24277869.
  12. ↑ Xu, Fang; Guo, Ganggang; Zhu, Wenbing; Fan, Liqing (2018-08-24). "Human sperm acrosome function assays are predictive of fertilization rate in vitro: a retrospective cohort study and meta-analysis". Reproductive Biology and Endocrinology. 16 (1): 81. doi: 10.1186/s12958-018-0398-y . ISSN   1477-7827. PMC   6109296 . PMID   30143014.
  13. 1 2 Gianaroli, Luca; Magli, M. Cristina; Ferraretti, Anna P; Crippa, Andor; Lappi, Michela; Capitani, Serena; Baccetti, Baccio (2010). "Birefringence characteristics in sperm heads allow for the selection of reacted spermatozoa for intracytoplasmic sperm injection". Fertility and Sterility. 93 (3): 807–13. doi: 10.1016/j.fertnstert.2008.10.024 . PMID   19064263.
  14. ↑ Miyazaki, R; Fukuda, M; Takeuchi, H; Itoh, S; Takada, M (2009). "Flow Cytometry to Evaluate Acrosome-Reacted Sperm". Archives of Andrology. 25 (3): 243–51. doi: 10.3109/01485019008987613 . PMID   2285347.
  15. ↑ Carver-Ward, J. A; Moran-Verbeek, I. M; Hollanders, J. M. G (1997). "Comparative flow cytometric analysis of the human sperm acrosome reaction using CD46 antibody and lectins". Journal of Assisted Reproduction and Genetics. 14 (2): 111–9. doi:10.1007/BF02765780. PMC   3454831 . PMID   9048242.
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