| Human fertilization | |
|---|---|
 Sperm about to enter the ovum with acrosomal head ready to penetrate thezona pellucida and fertilize the egg | |
 Illustration depictingovulation and fertilization | |
| Details | |
| Days | 0 |
| Precursor | Gametes |
| Gives rise to | Zygote |
| Anatomical terminology | |
| Part ofa series on |
| Human growth and development |
|---|
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| Stages |
| Biological milestones |
| Development and psychology |
Human fertilization is the union of anegg andsperm, occurring primarily in theampulla of the fallopian tube.[1] The result of this union leads to the production of a fertilized egg called azygote, initiatingembryonic development. Scientists discovered the dynamics of human fertilization in the 19th century.[2]
The process offertilization involves a sperm fusing with an ovum. The most common sequence begins withejaculation duringcopulation, follows withovulation, and finishes with fertilization. Various exceptions to this sequence are possible, includingartificial insemination,in vitro fertilization, external ejaculation without copulation, or copulation shortly after ovulation.[3][4] Upon encountering the secondaryoocyte, theacrosome of the sperm produces enzymes which allow it to burrow through the outer shell called thezona pellucida of the egg. The sperm plasma then fuses with the egg's plasma membrane and theirnuclei 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.
Fertilization was not understood in antiquity.Hippocrates believed that the embryo was the product of male semen and a female factor.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 thepreformationistPythagoras. Aristotle argued for form and function emerging gradually, in a mode called by him asepigenetic.[6] In 1651,William Harvey refuted Aristotle's idea thatmenstrual blood could beinvolved in the formation of afetus, asserting that eggs from the female were somehow caused to become a fetus as a result ofsexual intercourse.[7]
Sperm cells were discovered in 1677 byAntonie 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 humanova was first observed in 1827 byKarl Ernst von Baer.[8] Only in 1876 didOscar Hertwig prove that fertilization is due to fusion of an egg and sperm cell.[5]
A common metaphor used to describe human fertilization is that ofsperm racing to meet an egg. Another commonly used metaphor is that of two halves making a whole.[10]
Fertilization occurs in the ampulla of thefallopian tube, the section that curves around the ovary.Capacitated sperm are attracted to progesterone, which is secreted from the cumulus cells surrounding the oocyte.[11] Progesterone binds to theCatSper 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.[12] Around 200 out of 200 million spermatozoa reach the ampulla.
At the beginning of the process, the sperm undergoes a series of changes, as freshly ejaculated sperm is unable or poorly able to fertilize.[13] The sperm must undergocapacitation in the female's reproductive tract, which increases its motility and hyperpolarizes its membrane, preparing it for theacrosome reaction, the enzymatic penetration of the egg's tough membrane, thezona pellucida, which surrounds the oocyte.[14]
The sperm binds through thecorona radiata, a layer of follicle cells on the outside of the secondaryoocyte. 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.[15]
Where the spermatozoon 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.[16]
After binding to the corona radiata the sperm reaches thezona pellucida, which is an extracellular matrix ofglycoproteins. 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.[17]
Some sperm cells consume theiracrosome 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.[18] It may be regarded as a mechanism ofkin 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.[19][20]
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 causescortical reaction to occur.[21]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 tohydrolyse into ZP2f — making the whole matrix hard and impermeable to sperm. This prevents fertilization of an egg by more than one sperm.[22]
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.
Theoocyte completes itssecond meiotic division. This results in a mature haploidovum and the release of a polar body.[23] The nucleus of the oocyte is called apronucleus in this process, to distinguish it from the nuclei that are the result of fertilization.
The sperm's tail andmitochondria degenerate with the formation of the male pronucleus. This is why all mitochondria in humans are of maternal origin. Still, a considerable amount ofRNA from the sperm is delivered to the resulting embryo and likely influences embryo development and the phenotype of the offspring.[24]
The sperm nucleus then fuses with the ovum, enabling fusion of their genetic material.
When the sperm enters theperivitelline space, asperm-specific protein Izumo on the head binds toJuno receptors on the oocyte membrane.[25] 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.[26] These two blocks ofpolyspermy are what prevent the zygote from having too much DNA.
The pronuclei migrate toward the center of the oocyte, rapidly replicating theirDNA as they do so to prepare the zygote for its firstmitotic division.[27]
Usually 23 chromosomes fromspermatozoon and 23 chromosomes from egg cellfuse (approximately half of spermatozoons carry X chromosome and the other half Y chromosome). Their membranes dissolve, leaving no barriers between the male and femalechromosomes. During this dissolution, amitotic 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.[27]
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 is the event most commonly used to mark the beginning point of life, in descriptions ofprenatal development of the embryo or fetus.[28] The resultant age is known asfertilization age,conceptional age,embryonic age,fetal age or(intrauterine) developmental (IUD)[29] age.
Gestational age, in contrast, takes the beginning of the lastmenstrual period (LMP) as the start point. By convention, gestational age is calculated by adding 14 days to fertilization age and vice versa.[30]
| Event | Gestational age (from the start of thelast menstrual period) | Fertilization age | Implantation age |
|---|---|---|---|
| Menstrual period begins | Day 1 of pregnancy | Not pregnant | Not pregnant |
| Hassex andovulates | 2 weeks pregnant | Not pregnant | Not pregnant |
| Fertilization;cleavage stage begins[31] | Day 15[31] | Day 1[31][32] | Not pregnant |
| Implantation ofblastocyst begins | Day 20 | Day 6[31][32] | Day 0 |
| Implantation finished | Day 26 | Day 12[31][32] | Day 6 (or Day 0) |
| Embryo stage begins; firstmissed period | 4 weeks | Day 15[31] | Day 9 |
| Primitive heart function can bedetected | 5 weeks, 5 days[31] | Day 26[31] | Day 20 |
| Fetal stage begins | 10 weeks, 1 day[31] | 8 weeks, 1 day[31] | 7 weeks, 2 days |
| First trimester ends | 13 weeks | 11 weeks | 10 weeks |
| Second trimester ends | 26 weeks | 24 weeks | 23 weeks |
| Childbirth | 39–40 weeks | 37–38 weeks[32]: 108 | 36–37 weeks |
Fertilization though usually occurs within a day ofovulation, which, in turn, occurs on average 14.6 days after the beginning of the preceding menstruation (LMP).[33] 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.[34] In a reference group representing all women, the 95% prediction interval of the LMP-to-ovulation is 8.2 to 20.5 days.[33]
The average time to birth has been estimated to be 268 days (38 weeks and two days) fromovulation, with astandard deviation of 10 days orcoefficient of variation of 3.7%.[35]
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 ofintraventricular hemorrhage inpremature babies treated withextracorporeal membrane oxygenation.[36]
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.
Pregnancy is well known to occur from such external ejaculation ...
