Human embryonic development
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. 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.
Human embryology is the study of this development during the first eight weeks after fertilization. The normal period of gestation is about nine months or 40 weeks.
The germinal stage refers to the time from fertilization through the development of the early embryo until implantation is completed in the uterus. The germinal stage takes around 10 days. During this stage, the zygote divides in a process called cleavage. A blastocyst is then formed and implants in the uterus. Embryogenesis continues with the next stage of gastrulation, when the three germ layers of the embryo are formed. The processes of histogenesis, neurulation, and organogenesis follow.
The entire process of embryogenesis involves coordinated spatial and temporal changes in gene expression, cell growth, and cellular differentiation. A nearly identical process occurs in other species, especially among chordates.
Germinal stage
Fertilization
Fertilization takes place when the spermatozoon has successfully entered the ovum and the two sets of genetic material carried by the gametes fuse together, resulting in the zygote. This usually takes place in the ampulla of one of the fallopian tubes. The zygote contains the combined genetic material carried by both the male and female gametes which consists of the 23 chromosomes from the nucleus of the ovum and the 23 chromosomes from the nucleus of the sperm. The 46 chromosomes undergo changes prior to the mitotic division which leads to the formation of the embryo having two cells.Successful fertilization is enabled by three processes, which also act as controls to ensure species-specificity. The first is that of chemotaxis which directs the movement of the sperm towards the ovum. Secondly, an adhesive compatibility between the sperm and the egg occurs. With the sperm adhered to the ovum, the third process of acrosomal reaction takes place; the front part of the spermatozoan head is capped by an acrosome which contains digestive enzymes to break down the zona pellucida and allow its entry. The entry of the sperm causes calcium to be released which blocks entry to other sperm cells. A parallel reaction takes place in the ovum called the zona reaction. This sees the release of cortical granules that release enzymes which digest sperm receptor proteins, thus preventing polyspermy. The granules also fuse with the plasma membrane and modify the zona pellucida in such a way as to prevent further sperm entry.
Cleavage
The beginning of the cleavage process is marked when the zygote divides through mitosis into two cells. This mitosis continues and the first two cells divide into four cells, then into eight cells and so on. Each division takes from 12 to 24 hours. The zygote is large compared to any other cell and undergoes cleavage without any overall increase in size. This means that with each successive subdivision, the ratio of nuclear to cytoplasmic material increases.Initially, the dividing cells, called blastomeres, are undifferentiated and aggregated into a sphere enclosed within the zona pellucida of the ovum. When eight blastomeres have formed, they start to compact. They begin to develop gap junctions, enabling them to develop in an integrated way and co-ordinate their response to physiological signals and environmental cues.
When the cells number around sixteen, the solid sphere of cells within the zona pellucida is referred to as a morula.
Blastulation
Cleavage itself is the first stage in blastulation, the process of forming the blastocyst. Cells differentiate into an outer layer of cells called the trophoblast, and an inner cell mass. With further compaction the individual outer blastomeres, the trophoblasts, become indistinguishable. They are still enclosed within the zona pellucida. This compaction serves to make the structure watertight, containing the fluid that the cells will later secrete. The inner mass of cells differentiate to become embryoblasts and polarise at one end. They close together and form gap junctions, which facilitate cellular communication. This polarisation leaves a cavity, the blastocoel, creating a structure that is now termed the blastocyst..The trophoblasts secrete fluid into the blastocoel. The resulting increase in size of the blastocyst causes it to hatch through the zona pellucida, which then disintegrates. This process is called zona hatching and it takes place on the sixth day of embryo development, immediately before the implantation process. The hatching of the human embryo is supported by proteases secreted by the cells of the blastocyst, which digest proteins of the zona pellucida, giving rise to a hole. Then, due to the rhythmic expansion and contractions of the blastocyst, an increase of the pressure inside the blastocyst itself occurs, the hole expands and finally the blastocyst can emerge from this rigid envelope.
The inner cell mass will give rise to the pre-embryo, the amnion, yolk sac and allantois, while the fetal part of the placenta will form from the outer trophoblast layer. The embryo plus its membranes is called the conceptus, and by this stage the conceptus has reached the uterus. The zona pellucida ultimately disappears completely, and the now exposed cells of the trophoblast allow the blastocyst to attach itself to the endometrium, where it will implant.
The formation of the hypoblast and epiblast, which are the two main layers of the bilaminar germ disc, occurs at the beginning of the second week. Both the embryoblast and the trophoblast will turn into two sub-layers. The inner cells will turn into the hypoblast layer, which will surround the other layer, called the epiblast, and these layers will form the embryonic disc that will develop into the embryo.
The trophoblast will also develop two sub-layers: the cytotrophoblast, which is in front of the syncytiotrophoblast, which in turn lies within the endometrium. Next, another layer called the exocoelomic membrane or Heuser's membrane will appear and surround the cytotrophoblast, as well as the primitive yolk sac. The syncytiotrophoblast will grow and will enter a phase called lacunar stage, in which some vacuoles will appear and be filled by blood in the following days. The development of the yolk sac starts with the hypoblastic flat cells that form the exocoelomic membrane, which will coat the inner part of the cytotrophoblast to form the primitive yolk sac. An erosion of the endothelial lining of the maternal capillaries by the syncytiotrophoblastic cells results in the formation of the maternal sinusoids from where the blood will begin to penetrate and flow into and through the trophoblastic lacunae to give rise to the uteroplacental circulation. Subsequently, new cells derived from yolk sac will be established between trophoblast and exocoelomic membrane and will give rise to extra-embryonic mesoderm, which will form the chorionic cavity.
At the end of the second week of development, some cells of the trophoblast penetrate and form rounded columns into the syncytiotrophoblast. These columns are known as primary villi. At the same time, other migrating cells form into the exocoelomic cavity a new cavity named the secondary or definitive yolk sac, smaller than the primitive yolk sac.
Implantation
After ovulation, the endometrial lining becomes transformed into a secretory lining in preparation of accepting the embryo. It becomes thickened, with its secretory glands becoming elongated, and is increasingly vascular. This lining of the uterine cavity is now known as the decidua, and it produces a great number of large decidual cells in its increased interglandular tissue. The blastomeres in the blastocyst are arranged into an outer layer called the trophoblast. The trophoblast then differentiates into an inner layer, the cytotrophoblast, and an outer layer, the syncytiotrophoblast. The cytotrophoblast contains cuboidal epithelial cells and is the source of dividing cells, and the syncytiotrophoblast is a syncytial layer without cell boundaries.The syncytiotrophoblast implants the blastocyst in the decidual epithelium by projections of chorionic villi, forming the embryonic part of the placenta. The placenta develops once the blastocyst is implanted, connecting the embryo to the uterine wall. The decidua here is termed the decidua basalis; it lies between the blastocyst and the myometrium and forms the maternal part of the placenta. The implantation is assisted by hydrolytic enzymes that erode the epithelium. The syncytiotrophoblast also produces human chorionic gonadotropin, a hormone that stimulates the release of progesterone from the corpus luteum. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can oxygenate and sustain the developing embryo. The uterus liberates sugar from stored glycogen from its cells to nourish the embryo. The villi begin to branch and contain blood vessels of the embryo. Other villi, called terminal or free villi, exchange nutrients. The embryo is joined to the trophoblastic shell by a narrow connecting stalk that develops into the umbilical cord to attach the placenta to the embryo.
Arteries in the decidua are remodelled to increase the maternal blood flow into the intervillous spaces of the placenta, allowing gas exchange and the transfer of nutrients to the embryo. Waste products from the embryo will diffuse across the placenta.
As the syncytiotrophoblast starts to penetrate the uterine wall, the inner cell mass also develops. The inner cell mass is the source of embryonic stem cells, which are pluripotent and can develop into any one of the three germ layer cells, and which have the potency to give rise to all the tissues and organs.