Human embryonic development

Human embryology is the study of human development during the first eight weeks after fertilization (fusion of sperm and oocyte). At the conclusion of the 8th week after fertilization, the developing embryo becomes a fetus. Most humans spend the first nine months (38 weeks or 266 days) of life within the uterus of the mother.

Human embryogenesis is the process of cell division and cellular differentiation of the human embryo that occurs during early stages of development. In biological terms, human development entails growth from a one celled zygote to an adult human being. Fertilization occurs when the sperm successfully enters the ovum's membrane. The genetic material of the sperm and egg then combine to form a single cell called a zygote and the germinal stage of prenatal development commences.[1] The germinal stage, refers to the time from fertilization, through the development of the early embryo, up until implantation. The germinal stage is over at about 10 days of gestation.[2]

During this stage, the fertilization creates a single-celled zygote, which is defined as an embryo because it contains a full complement of genetic material. In humans, the embryo is referred to as a fetus in the later stages of prenatal development. The transition from embryo to fetus is arbitrarily defined as occurring 8 weeks after fertilization. In comparison to the embryo, the fetus has more recognizable external features, and a more complete set of developing internal organs. The entire process involves coordinated spatial and temporal changes in gene expression, cell growth and differentiation. A nearly identical process occurs in other species, especially among chordates.


Human fertilization is the union of a female oocyte (egg) and male sperm, usually occurring in the ampulla of the fallopian tube to form the zygote (single diploid cell). It constitutes the penetration of the oocyte (egg) by a sperm succeeded by fusion of their genetic material. This genetic material consists of the 23 chromosomes contained in the nucleus of the ovum and 23 chromosomes from the nucleus of the sperm. The 46 chromosomes undergo changes prior to the mitotic division which leads to the formation of an embryo having two cells. The fertilized ovum thus begins to divide into several cells, i.e. it starts to undergo cleavage. The two daughter cells are still surrounded by zona pellucida.


A human develops from a single diploid cell called a zygote, which results from the fusion of two reproductive cells; an ovum (egg) being fertilized by a single spermatozoon (sperm). The cell is surrounded by a strong membrane of glycoproteins called the zona pellucida (membrane derived from the ovum) which the successful sperm has managed to penetrate.

The zygote undergoes cleavage, increasing the number of cells within the zona pellucida. After the 8-cell stage, embryos undergo what is called compaction, where the cells bind tightly to each other, forming a compact sphere. After compactation, the embryo is in the morula stage (32 cells). Cavitation occurs next, where the outermost layer of cells - the trophoblast - secrete fluid into the morula.

As a consequence of this, when the number of cells reaches 40 to 150, a central, fluid-filled cavity (blastocoel) has been formed. The zona pellucida begins to degenerate, allowing the embryo to increase its volume. This stage in the developing embryo, reached after four to six days, is the blastocyst (akin to the blastula stage), and lasts approximately until implantation in the uterus, and is referred to as the preimplantation phase of development.

Each cell of the preimplantation embryo is totipotent. That is, each cell has the potential to form all of the different cell types in the developing embryo. This totipotency means that some cells can be removed from the preimplantation embryo and the remaining cells will compensate for their absence. This has allowed the development of a technique known as preimplantation genetic diagnosis (PGD), whereby a small number of cells from the preimplantation embryo created by IVF, can be removed by biopsy and subjected to genetic diagnosis. This allows embryos that are not affected by defined genetic diseases to be selected and then transferred to the mother's uterus.

Blastocyst differentiation

The blastocyst is characterized by a group of cells, called the inner cell mass (also called embryoblast) and the mentioned trophoblast (the outer cells), and a blastocyst cavity (blastocoel).

The inner cell mass gives rise to the embryo proper, the amnion, yolk sac and allantois, while the trophoblast will eventually form the placenta. The blastocyst can be thought of as a ball of a (mostly single) layer of trophoblast cells, with the inner cell mass attached to this ball's inner wall. The embryo plus its membranes is called the conceptus. By this stage the conceptus is in the uterus. The zona pellucida ultimately disappears completely, allowing the blastocyst to invade the endometrium, performing implantation.


The trophoblast then differentiates into two distinct layers: the inner is the cytotrophoblast (containing cell boundaries) consisting of cuboidal cells that are the source of dividing cells, and the outer is the syncytiotrophoblast (no cell boundaries).

The syncytiotrophoblast implants the blastocyst in the endometrium (innermost epithelial lining) of the uterus by forming finger-like projections called chorionic villi that make their way into the uterus, and spaces called lacunae that fill up with the mother's blood. This is assisted by hydrolytic enzymes that erode the epithelium. The syncytiotrophoblast also produces human chorionic gonadotropin (hCG), a hormone that "notifies" the mother's body that she is pregnant, preventing menstruation by sustaining the function of the corpus luteum. The villi begin to branch, and contain blood vessels of the fetus that allow gas exchange between mother and child.

Inner cell mass differentiation

While the syncytiotrophoblast starts to penetrate into the wall of the uterus, the inner cell mass (embryoblast) also develops.

The embryoblast forms a bilaminar (two layered) embryo, composed of the epiblast and the hypoblast. The epiblast is adjacent to the trophoblast and made of columnar cells; the hypoblast is closest to the blastocyst cavity, and made of cuboidal cells. The epiblast, now called primitive ectoderm will perform gastrulation, approximately at day 16 (week 3) after fertilization. In this process, it gives rise to all three germ layers of the embryo, of which the top one (called the ectoderm) will give rise to the embryo's outermost layer of skin, central and peripheral nervous systems, eyes, inner ear, and many connective tissues.[3] The heart and the beginning of the circulatory system as well as the bones, muscles and kidneys are made up from the mesoderm (the middle layer). The inner layer of the embryo will serve as the starting point for the development of the lungs, intestine and bladder. This layer is referred to as the endoderm. An embryo at 5 weeks is normally between 116 and 18 inch (1.6 and 3.2 mm) in length.

The hypoblast, or primitive endoderm, will give rise to extraembryonic structures only, such as the lining of the primary (primitive) yolk sac (exocoelomic cavity). The segregation of the inner cell mass into the epiblast and hypoblast is the earliest developmental event that predicts the dorsal-ventral axis of the embryo.

Cavity formation

By separating from the trophoblast, the epiblast forms a new cavity, the amniotic cavity. This is lined by the amnionic membrane, with cells that come from the epiblast (called amnioblasts). Some hypoblast cells migrate along the inner cytotrophoblast lining of the blastocoel, secreting an extracellular matrix along the way. These hypoblast cells and extracellular matrix are called Heuser's membrane (or exocoelomic membrane), and the blastocoel is now called the primary yolk sac (or exocoelomic cavity).

Cytotrophoblast cells and cells of Heuser's membrane continue secreting extracellular matrix between them. This matrix is called the extraembryonic reticulum. Cells of the epiblast migrate along the outer edges of this reticulum and form the extraembryonic mesoderm, which makes it difficult to maintain the extraembryonic reticulum. Soon pockets form in the reticulum, which ultimately coalesce to form the chorionic cavity or extraembryonic coelom.

Another layer of cells leaves the hypoblast and migrates along the inside of the primary yolk sac. The primary yolk sac is pushed to the opposite side of the embryo (the abembryonic pole), while a new cavity forms, the secondary or definitive yolk sac. The remnants of the primary yolk sac are called exocoelomic vesicles (exocoelomic cysts).


Toxic exposures during the first two weeks following fertilization (second and third weeks of gestational age) may cause prenatal death but do not cause developmental defects. Instead, the body performs a miscarriage. On the other hand, subsequent toxic exposures in the embryonic period often cause major congenital malformations, since the precursors of the major organ systems are developing.

See also


External links

  • Photo of blastocyst in utero
  • Slideshow: In the Womb
  • Online course in embryology for medicine students developed by the universities of Fribourg, Lausanne and Bern
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