Human fertilization

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Human fertilization
The sperm and ovum during fertilization.svg
Sperm about to enter the ovum with acrosomal head ready to penetrate the zona pellucida and fertilize the egg
Blausen 0404 Fertilization.png
Illustration depicting ovulation and fertilization
Details
Days0
Precursor Gametes
Gives rise to Zygote
Anatomical terminology

Human fertilization is the union of an egg and sperm, occurring primarily in the ampulla of the fallopian tube. [1] 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. [2]

Contents

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] Upon encountering the secondary oocyte, the acrosome of the sperm produces enzymes which allow it to burrow through the outer shell called the zona pellucida of the egg. The sperm plasma then fuses with the egg's plasma membrane and their nuclei fuse, triggering the sperm head to disconnect from its flagellum as the egg travels down the fallopian tube to reach the uterus.

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

History

Fertilization was not understood in antiquity. Hippocrates believed that the embryo was the product of male semen and a female factor. But Aristotle held that only male semen gave rise to an embryo, while the female only provided a place for the embryo to develop, [5] a concept he acquired from the preformationist Pythagoras. Aristotle argued for form and function emerging gradually, in a mode called by him as epigenetic. [6] In 1651 William Harvey refuted Aristotle's idea that menstrual blood could be involved in the formation of a fetus, asserting that eggs from the female were somehow caused to become a fetus as a result of sexual intercourse. [7] Sperm cells were discovered in 1677 by Antonie van Leeuwenhoek, who believed that Aristotle had been proven correct. [8] Some observers believed they could see an entirely pre-formed little human body in the head of a sperm. [9] The human ova was first observed in 1827 by Karl Ernst von Baer. [8] Only in 1876 did Oscar Hertwig prove that fertilization is due to fusion of an egg and sperm cell. [5]

Sperm and oocyte meet

Ampulla

Fertilization occurs in the ampulla of the fallopian tube, the section that curves around the ovary. Capacitated sperm are attracted to progesterone, which is secreted from the cumulus cells surrounding the oocyte. [10] Progesterone binds to the CatSper receptor on the sperm membrane and increases intracellular calcium levels, causing hyperactive motility. The sperm will continue to swim towards higher concentrations of progesterone, effectively guiding it to the oocyte. [11] Around 200 out of 200 million spermatozoa reach the ampulla.

Sperm preparation

The sperm entering the ovum using acrosomal enzymes to dissolve the gelatinous envelope (zona pellucida)of the oocyte. Egg cell fertilization - Zygote.png
The sperm entering the ovum using acrosomal enzymes to dissolve the gelatinous envelope (zona pellucida)of the oocyte.

At the beginning of the process, the sperm undergoes a series of changes, as freshly ejaculated sperm is unable or poorly able to fertilize. [12] The sperm must undergo capacitation in the female's reproductive tract, which increases its motility and hyperpolarizes its membrane, preparing it for the acrosome reaction, the enzymatic penetration of the egg's tough membrane, the zona pellucida, which surrounds the oocyte. [13]

Corona radiata

The sperm binds through the corona radiata, a layer of follicle cells on the outside of the secondary oocyte. The corona radiata sends out chemicals that attract the sperm in the fallopian tube to the oocyte. It lies above the zona pellucida, a membrane of glycoproteins that surrounds the oocyte. [14]

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. [15]

Zona pellucida and acrosome reaction

After binding to the corona radiata the sperm reaches the zona pellucida, which is an extracellular matrix of glycoproteins. A ZP3 glycoprotein on the zona pellucida binds to a receptor on the cell surface of the sperm head. This binding triggers the acrosome to burst, releasing acrosomal enzymes that help the sperm penetrate through the thick zona pellucida layer surrounding the oocyte, ultimately gaining access to the egg's cell membrane. [16]

Some sperm cells consume their acrosome prematurely on the surface of the egg cell, facilitating the penetration by other sperm cells. As a population, mature haploid sperm cells have on average 50% genome similarity, so the premature acrosomal reactions aid fertilization by a member of the same cohort. [17] It may be regarded as a mechanism of kin selection.

Recent studies have shown that the egg is not passive during this process. In other words, they too appear to undergo changes that help facilitate such interaction. [18] [19]

Fusion

Fertilization and implantation in humans. 2904 Preembryonic Development-02.jpg
Fertilization and implantation in humans.

Cortical reaction

After the sperm enters the cytoplasm of the oocyte, the tail and the outer coating of the sperm disintegrate. The fusion of sperm and oocyte membranes causes cortical reaction to occur. [20] 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 glycoproteins 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. [21]

Fusion of genetic material

Preparation

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 haploid ovum and the release of a polar body. [22] The nucleus of the oocyte is called a pronucleus in this process, to distinguish it from the nuclei that are the result of fertilization.

Drawing of an ovum Ovum Diagram.svg
Drawing of an ovum

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. [23]

Fusion

The sperm nucleus then fuses with the ovum, enabling fusion of their genetic material.

Blocks of polyspermy

When the sperm enters the perivitelline space, a sperm-specific protein Izumo on the head binds to Juno receptors on the oocyte membrane. [24] Once it is bound, two blocks to polyspermy then occur. After approximately 40 minutes, the other Juno receptors on the oocyte are lost from the membrane, causing it to no longer be fusogenic. Additionally, the cortical reaction will happen which is caused by ovastacin binding and cleaving ZP2 receptors on the zona pellucida. [25] These two blocks of polyspermy are what prevent the zygote from having too much DNA.

Replication

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. [26]

Mitosis

Usually 23 chromosomes from spermatozoon and 23 chromosomes from egg cell fuse (approximately half of spermatozoons carry X chromosome and the other half Y chromosome [27] ). 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. [26]

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.[ citation needed ]

Fertilization age

Fertilization is the event most commonly used to mark the beginning point of life, in descriptions of prenatal development of the embryo or fetus. [28] The resultant age is known as fertilization age, fertilizational age, conceptional age, embryonic age, fetal age or (intrauterine) developmental (IUD) [29] age.

Gestational age, in contrast, takes the beginning of the last menstrual period (LMP) as the start point. By convention, gestational age is calculated by adding 14 days to fertilization age and vice versa. [30] Fertilization though usually occurs within a day of ovulation, which, in turn, occurs on average 14.6 days after the beginning of the preceding menstruation (LMP). [31] 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. [32] In a reference group representing all women, the 95% prediction interval of the LMP-to-ovulation is 8.2 to 20.5 days. [31]

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%. [33]

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. [34]

Diseases affecting human fertility

Various disorders can arise from defects in the fertilization process. Whether that results in the process of contact between the sperm and egg, or the state of health of the biological parent carrying the zygote cell. The following are a few of the diseases that can occur and be present during the process.

See also

Related Research Articles

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

A spermatozoon is a motile sperm cell produced by male animals relying on internal fertilization. A spermatozoon is a moving form of the haploid cell that is the male gamete that joins with an ovum to form a zygote.

<span class="mw-page-title-main">Zygote</span> Diploid eukaryotic cell formed by fertilization 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 of a new individual organism. The sexual fusion of haploid cells is called karyogamy, the result of which is the formation of a diploid cell called the zygote or zygospore.

<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">Menstrual cycle</span> Natural changes in the human female reproductive system

The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eggs and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive an embryo. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a median length of 28 days. Menarche usually occurs around the age of 12 years; menstrual cycles continue for about 30–45 years.

<span class="mw-page-title-main">Egg cell</span> Female reproductive cell in most anisogamous organisms

The egg cell or ovum is the female reproductive cell, or gamete, in most anisogamous organisms. The term is used when the female gamete is not capable of movement (non-motile). If the male gamete (sperm) is capable of movement, the type of sexual reproduction is also classified as oogamous. A nonmotile female gamete formed in the oogonium of some algae, fungi, oomycetes, or bryophytes is an oosphere. When fertilized, the oosphere becomes the oospore.

<span class="mw-page-title-main">Acrosome reaction</span> Sperm-meets-egg process

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.

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 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.

<span class="mw-page-title-main">Oogenesis</span> Egg cell production process

Oogenesis or ovogenesis is the differentiation of the ovum into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated in the embryonic stage.

<span class="mw-page-title-main">Female reproductive system</span> Reproductive system of female humans

The human female reproductive system is made up of the internal and external sex organs that function in the reproduction of new offspring. The reproductive system is immature at birth and develops at puberty to be able to release matured ova from the ovaries, facilitate their fertilization, and create a protective environment for the developing fetus during pregnancy. The female reproductive tract is made of several connected internal sex organs—the vagina, uterus, and fallopian tubes—and is prone to infections. The vagina allows for sexual intercourse, and is connected to the uterus at the cervix. The uterus accommodates the embryo by developing the uterine lining.

<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.

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">Luteal phase</span> The latter part of the menstrual cycle associated with ovulation and an increase in progesterone

The menstrual cycle is on average 28 days in length. It begins with menses during the follicular phase, followed by ovulation and ending with the luteal phase. Unlike the follicular phase which can vary in length among individuals, the luteal phase is typically fixed at approximately 14 days and is characterized by changes to hormone levels, such as an increase in progesterone and estrogen levels, decrease in gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), changes to the endometrial lining to promote implantation of the fertilized egg, and development of the corpus luteum. In the absence of fertilization by sperm, the corpus luteum degenerates leading to a decrease in progesterone and estrogen, an increase in FSH and LH, and shedding of the endometrial lining (menses) to begin the menstrual cycle again.

<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.

<span class="mw-page-title-main">Human reproduction</span> Procreative biological processes of humanity

Human reproduction is sexual reproduction that results in human fertilization to produce a human offspring. It typically involves sexual intercourse between a sexually mature human male and female. During sexual intercourse, the interaction between the male and female reproductive systems results in fertilization of the ovum by the sperm to form a zygote. While normal cells contain 46 chromosomes, gamete cells only contain 23 single 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 it 46 chromosomes. The zygote then undergoes a defined development process that is known as human embryogenesis, and this starts the typical 9-month gestation period that is followed by childbirth. The fertilization of the ovum may be achieved by artificial insemination methods, which do not involve sexual intercourse. Assisted reproductive technology also exists.

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 the oolemma is a fluid-filled perivitelline space.

<span class="mw-page-title-main">Human embryonic development</span> Development and formation of the human embryo

Human embryonic development or human embryogenesis is the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of development. In biological terms, the development of the human body entails growth from a one-celled zygote to an adult human being. Fertilization occurs when the sperm cell successfully enters and fuses with an egg cell (ovum). The genetic material of the sperm and egg then combine to form the single cell zygote and the germinal stage of development commences. Human embryonic development covers the first eight weeks of development, which have 23 stages, called Carnegie stages. At the beginning of the ninth week, the embryo is termed a fetus. In comparison to the embryo, the fetus has more recognizable external features and a more complete set of developing organs.

<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">Fallopian tube</span> Tubes in the human female reproductive system

The fallopian tubes, also known as uterine tubes, oviducts or salpinges, are paired tubular sex organs in the human female body that stretch from the ovaries to the uterus. The fallopian tubes are part of the female reproductive system. In other vertebrates, they are only called oviducts.

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.

References

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