Human fertilization

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The acrosome reaction for a sea urchin, a similar process. Note that the picture shows several stages of one and the same spermatozoon - only one penetrates the ovum Acrosome reaction diagram en.svg
The acrosome reaction for a sea urchin, a similar process. Note that the picture shows several stages of one and the same spermatozoon - only one penetrates the ovum
Illustration depicting ovulation and fertilization. Blausen 0404 Fertilization.png
Illustration depicting ovulation and fertilization.
The sperm entering the ovum using the acrosome head to break down the zona pellucida. The sperm and ovum during fertilization.svg
The sperm entering the ovum using the acrosome head to break down the zona pellucida.

Human fertilization is the union of a human egg and sperm, usually occurring in the ampulla of the fallopian tube. [1] The result of this union is the production of a zygote cell, or fertilized egg, initiating prenatal development. Scientists discovered the dynamics of human fertilization in the nineteenth century. [2]

Spermatozoon male reproductive 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.

Zygote single diploid eukaryotic cell formed by a fertilization event between two gametes

A zygote is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information necessary to form a new individual. In multicellular organisms, the zygote is the earliest developmental stage. In single-celled organisms, the zygote can divide asexually by mitosis to produce identical offspring.

Prenatal development includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal development until birth.


The process of fertilization involves a sperm fusing with an ovum. The most common sequence begins with ejaculation during copulation, follows with ovulation, and finishes with fertilization. Various exceptions to this sequence are possible, including artificial insemination, in vitro fertilization, external ejaculation without copulation, or copulation shortly after ovulation. [3] [4] [5] Upon encountering the secondary oocyte, the acrosome of the sperm produces enzymes which allow it to burrow through the outer jelly coat of the egg. The sperm plasma, then fuses with the egg's plasma membrane, the sperm head disconnects from its flagellum and the egg travels down the Fallopian tube to reach the uterus.

Ejaculation The expulsion of seminal fluid, thick white fluid containing spermatozoa, from the male genital tract.

Ejaculation is the discharge of semen from the male reproductory tract, usually accompanied by orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential component of natural conception. In rare cases, ejaculation occurs because of prostatic disease. Ejaculation may also occur spontaneously during sleep. Anejaculation is the condition of being unable to ejaculate. Ejaculation is usually very pleasurable for men; dysejaculation is an ejaculation that is painful or uncomfortable. Retrograde ejaculation is the condition where semen travels backwards into the bladder rather than out the urethra.

Sexual intercourse any act of set of actions performed for reproduction, sexual pleasure or both

Sexual intercourse is principally the insertion and thrusting of the penis, usually when erect, into the vagina for sexual pleasure, reproduction, or both. This is also known as vaginal intercourse or vaginal sex. Other forms of penetrative sexual intercourse include anal sex, oral sex, fingering, and penetration by use of a dildo. These activities involve physical intimacy between two or more individuals and are usually used among humans solely for physical or emotional pleasure and can contribute to human bonding.

Ovulation The release of a mature ovum/oocyte from an ovary.

Ovulation is the release of eggs from the ovaries. In humans, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized by sperm. In addition, the uterine lining (endometrium) is thickened to be able to receive a fertilized egg. If no conception occurs, the uterine lining as well as blood will be shed during menstruation.

In vitro fertilization (IVF) is a process by which egg cells are fertilized by sperm outside the womb, in vitro .

<i>In vitro</i> test-tube experiments

In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from in vitro experiments may not fully or accurately predict the effects on a whole organism. In contrast to in vitro experiments, in vivo studies are those conducted in animals, including humans, and whole plants.


Corona radiata

The sperm binds through the corona radiata, a layer of follicle cells on the outside of the secondary oocyte. Fertilization occurs when the nucleus of both a sperm and an egg fuse to form a diploid cell, known as zygote. The successful fusion of gametes forms a new organism.

Corona radiata (embryology) cellular mantle around egg cell

The corona radiata is the innermost layer of the cells of the cumulus oophorus and is directly adjacent to the zona pellucida, the inner protective glycoprotein layer of the ovum. Its main purpose in many animals is to supply vital proteins to the cell. It is formed by follicle cells adhering to the oocyte before it leaves the ovarian follicle, and originates from the squamous granulosa cells present at the primordial stage of follicular development. The corona radiata is formed when the granulosa cells enlarge and become cuboidal, which occurs during the transition from the primordial to primary stage. These cuboidal granulosa cells, also known as the granulosa radiata, form more layers throughout the maturation process, and remain attached to the zona pellucida after the ovulation of the Graafian follicle. For fertilization to occur, sperm cells rely on hyaluronidase to disperse the corona radiata from the zona pellucida of the secondary (ovulated) oocyte, thus permitting entry into the perivitelline space and allowing contact between the sperm cell and the nucleus of the oocyte.

An oocyte, oöcyte, ovocyte, or rarely ocyte, 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 the ovary during female gametogenesis. The female germ cells produce a primordial germ cell (PGC), which then undergoes mitosis, forming oogonia. During oogenesis, the oogonia become primary oocytes. An oocyte is a form of genetic material that can be collected for cryoconservation. Cryoconservation of animal genetic resources have been put into action as a means of conserving traditional livestock.

Cone of attraction and perivitelline membrane

Where the spermatozoan is about to pierce, the yolk (ooplasm) is drawn out into a conical elevation, termed the cone of attraction or reception cone. Once the spermatozoon has entered, the peripheral portion of the yolk changes into a membrane, the perivitelline membrane, which prevents the passage of additional spermatozoa. [6]

Sperm preparation

At the beginning of the process, the sperm undergoes a series of changes, as freshly ejaculated sperm is unable or poorly able to fertilize. [7] The sperm must undergo capacitation in the female's reproductive tract over several hours, which increases its motility and destabilizes its membrane, preparing it for the acrosome reaction, the enzymatic penetration of the egg's tough membrane, the zona pellucida, which surrounds the oocyte.

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 superior 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.

Acrosome reaction The discharge, by sperm, of a single, anterior secretory granule following the sperms attachment to the zona pellucida surrounding the oocyte. The process begins with the fusion of the outer acrosomal membrane with the sperm plasma membrane and ends

During fertilization, a sperm must first fuse with the plasma membrane and then penetrate the female egg cell in order to fertilize it. Fusing to the egg cell usually causes little problem, whereas penetrating through the egg's hard shell or extracellular matrix can present more of a problem to the sperm. 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. The acrosome is a cap-like structure over the anterior half of the sperm's head.

Zona pellucida

The zona pellucida is a glycoprotein layer surrounding the plasma membrane of mammalian oocytes. It is a vital constitutive part of the oocyte. The zona pellucida first appears in unilaminar primary oocytes. It is secreted by both the oocyte and the ovarian follicles. The zona pellucida is surrounded by the cumulus oophorus. The cumulus is composed of cells that care for the egg when it is emitted from the ovary.

Zona pellucida

After binding to the corona radiata the sperm reaches the zona pellucida, which is an extra-cellular matrix of glycoproteins. A special complementary molecule on the surface of the sperm head binds to a ZP3 glycoprotein in the zona pellucida. This binding triggers the acrosome to burst, releasing enzymes that help the sperm get through the zona pellucida.

Some sperm cells consume their acrosome prematurely on the surface of the egg cell, facilitating the penetration by other sperm cells. As a population, sperm cells have on average 50% genome similarity so the premature acrosomal reactions aid fertilization by a member of the same cohort. [8] It may be regarded as a mechanism of kin selection.

Recent studies have shown that the egg is not passive during this process. [9] [10]

Cortical reaction

Once the sperm cells find their way past the zona pellucida, the cortical reaction occurs. Cortical granules inside the secondary oocyte fuse with the plasma membrane of the cell, causing enzymes inside these granules to be expelled by exocytosis to the zona pellucida. This in turn causes the glyco-proteins in the zona pellucida to cross-link with each other — i.e. the enzymes cause the ZP2 to hydrolyse into ZP2f — making the whole matrix hard and impermeable to sperm. This prevents fertilization of an egg by more than one sperm. The cortical reaction and acrosome reaction are both essential to ensure that only one sperm will fertilize an egg. [11]


Fertilization and implantation in humans. Human Fertilization.png
Fertilization and implantation in humans.

After the sperm enters the cytoplasm of the oocyte (also called ovocyte), the tail and the outer coating of the sperm disintegrate and the cortical reaction takes place, preventing other sperm from fertilizing the same egg. The oocyte now undergoes its second meiotic division producing the haploid ovum and releasing a polar body. The sperm nucleus then fuses with the ovum, enabling fusion of their genetic material.

Cell membranes

The fusion of cell membranes of the secondary oocyte and sperm takes place.


In preparation for the fusion of their genetic material both the oocyte and the sperm undergo transformations as a reaction to the fusion of cell membranes.

The oocyte completes its second meiotic division. This results in a mature ovum. The nucleus of the oocyte is called a pronucleus in this process, to distinguish it from the nuclei that are the result of fertilization.

The sperm's tail and mitochondria degenerate with the formation of the male pronucleus. This is why all mitochondria in humans are of maternal origin. Still, a considerable amount of RNA from the sperm is delivered to the resulting embryo and likely influences embryo development and the phenotype of the offspring. [12]


The pronuclei migrate toward the center of the oocyte, rapidly replicating their DNA as they do so to prepare the zygote for its first mitotic division. [13]


Usually 23 chromosomes from spermatozoon and 23 chromosomes from egg cell fuse (half of spermatozoons carry X chromosome and the other half Y chromosome [14] ). Their membranes dissolve, leaving no barriers between the male and female chromosomes. During this dissolution, a mitotic spindle forms between them. The spindle captures the chromosomes before they disperse in the egg cytoplasm. Upon subsequently undergoing mitosis (which includes pulling of chromatids towards centrioles in anaphase) the cell gathers genetic material from the male and female together. Thus, the first mitosis of the union of sperm and oocyte is the actual fusion of their chromosomes. [13]

Each of the two daughter cells resulting from that mitosis has one replica of each chromatid that was replicated in the previous stage. Thus, they are genetically identical.

Fertilization age

Fertilization is the event most commonly used to mark the zero point in descriptions of prenatal development of the embryo or fetus. The resultant age is known as fertilization age, fertilizational age, embryonic age, fetal age or (intrauterine) developmental (IUD) [15] age.

Gestational age, in contrast, takes the beginning of the last menstrual period (LMP) as the zero point. By convention, gestational age is calculated by adding 14 days to fertilization age and vice versa. [16] In fact, however, fertilization usually occurs within a day of ovulation, which, in turn, occurs on average 14.6 days after the beginning of the preceding menstruation (LMP). [17] There is also considerable variability in this interval, with a 95% prediction interval of the ovulation of 9 to 20 days after menstruation even for an average woman who has a mean LMP-to-ovulation time of 14.6. [18] In a reference group representing all women, the 95% prediction interval of the LMP-to-ovulation is 8.2 to 20.5 days. [17]

The average time to birth has been estimated to be 268 days (38 weeks and two days) from ovulation, with a standard deviation of 10 days or coefficient of variation of 3.7%. [19]

Fertilization age is sometimes used postnatally (after birth) as well to estimate various risk factors. For example, it is a better predictor than postnatal age for risk of intraventricular hemorrhage in premature babies treated with extracorporeal membrane oxygenation. [20]


Various disorders can arise from defects in the fertilization process.

However, some researchers have found[ citation needed ] that in rare pairs of fraternal twins, their origin might have been from the fertilization of one egg cell from the mother and eight sperm cells from the father. This possibility has been investigated by computer simulations of the fertilization process.

See also

Related Research Articles

Gamete haploid cell that fuses with another haploid cell during fertilization (conception) in organisms that sexually reproduce

A gamete is a haploid cell that fuses with another haploid cell during fertilization (conception) in organisms that sexually reproduce. In species that produce two morphologically distinct types of gametes, and in which each individual produces only one type, a female is any individual that produces the larger type of gamete—called an ovum —and a male produces the smaller tadpole-like type—called a sperm. In short a gamete is an egg or a sperm. This is an example of anisogamy or heterogamy, the condition in which females and males produce gametes of different sizes. In contrast, isogamy is the state of gametes from both sexes being the same size and shape, and given arbitrary designators for mating type. The name gamete was introduced by the Austrian biologist Gregor Mendel. Gametes carry half the genetic information of an individual, one ploidy of each type, and are created through meiosis.

Fertilisation union of gametes of opposite sexes during the process of sexual reproduction to form a zygot

Fertilisation or fertilization, also known as generative fertilisation, insemination, pollination, fecundation, syngamy and impregnation, is the fusion of gametes to initiate the development of a new individual organism or offspring. This 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.

Egg cell haploid female reproductive cell or gamete

The egg cell, or ovum, is the female reproductive cell (gamete) in oogamous organisms. The egg cell is typically not capable of active movement, and it is much larger than the motile sperm cells. When egg and sperm fuse, a diploid cell is formed, which rapidly grows into a new organism.

In biology, polyspermy describes an egg that has been fertilized 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 inviable 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.

Cortical reaction

The cortical reaction is a process initiated during fertilization by the release of cortical granules from the egg, which 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.

Polar body small haploid cell that is formed concomitantly as an egg cell during oogenesis, but which generally does not have the ability to be fertilized

A polar body is a small haploid cell that is formed concomitantly as an egg cell during oogenesis, but which generally does not have the ability to be fertilized. When certain diploid cells in animals undergo cytokinesis after meiosis to produce egg cells, they sometimes divide unevenly. Most of the cytoplasm is segregated into one daughter cell, which becomes the egg or ovum, while the smaller polar bodies only get a small amount of cytoplasm. They frequently die (apoptosis) and disappear, but in some cases they remain and can be important in the life cycle of the organism.

Human reproduction

Human reproduction is any form of sexual reproduction resulting in human fertilization, typically involving sexual intercourse between a man and a woman. During sexual intercourse, the interaction between the male and female reproductive systems results in fertilization of the woman's ovum by the man's sperm. These are specialized reproductive cells called gametes, created in a process called meiosis. While normal cells contains 46 chromosomes, 23 pairs, gamete cells only contain 23 chromosomes, and it is when these two cells merge into one zygote cell that genetic recombination occurs and the new zygote contains 23 chromosomes from each parent, giving them 23 pairs. A typical 9-month gestation period is followed by childbirth. The fertilization of the ovum may be achieved by artificial insemination methods, which do not involve sexual intercourse.

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.

ZP2 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.

Perivitelline space The space between the membrane of an oocyte and a surrounding membranous structure (zona pellucida or perivitelline membrane).

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. Polysaccharides released in the granules cause the space to swell, pushing the zona pellucida farther from the oocyte. The hydrolytic enzymes released by the granules cause the zona reaction, which removes the ZP3 ligands from the zona pellucida.

Reproductive immunology refers to a field of medicine that studies interactions between the immune system and components related to the reproductive system, such as maternal immune tolerance towards the fetus, or immunological interactions across the blood-testis barrier. The concept has been used by fertility clinics to explain the fertility problems, recurrent miscarriages and pregnancy complications observed when this state of immunological tolerance is not successfully achieved. Immunological therapy is the new up and coming method for treating many cases of previously "unexplained infertility" or recurrent miscarriage.

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

Cortical granule A secretory vesicle that is stored under the cell membrane of an egg. These vesicles fuse with the egg plasma membrane as part of egg activation and are part of the block to polyspermy.

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.


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