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The blastocyst is a structure formed in the early development of mammals. In humans, its formation begins 5 days after fertilization during the germinal stage of development. It possesses an inner cell mass (ICM) which subsequently forms the embryo. The outer layer of cells of the blastocyst are called the trophoblast. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. The trophoblast gives rise to the placenta.

The human blastocyst comprises 200-300 cells following rapid cleavage throughout this stage. This group of cells embeds itself into the endometrium of the uterine wall where it will undergo later developmental processes, including gastrulation.

The use of blastocysts in in-vitro fertilization (IVF) involves culturing a fertilized egg for five days before implanting it into the uterus. It can be more a viable method of fertility treatment than traditional IVF.

Development cycle
During human embryogenesis, the blastocyst arises from the morula in the uterus, 5 days after fertilization. The early embryo undergoes cell differentiation and structural changes to become the blastocyst. It is then prepared for implantation into the uterine wall 6 days after fertilization. Implantation marks the end of the germinal stage and the beginning of the embryonic stage of development.

Blastocyst formation
The morula, which precedes the blastocyst, is an early embryo comprised of 16 undifferentiated cells. Shortly following the morula's entry into the uterus from the Fallopian tube, the morula becomes the blastocyst through cellular differentiation and cavitation. The morula's cells differentiate into two types: an inner cell mass growing on the interior of the blastocoel and trophoblast cells growing on the exterior. The animal pole refers to the side of the blastocyst where the ICM resides, while the vegetal pole is on the opposite side. Cavitation is the process by which the outer trophoblast cells secrete fluid inside the embryo. The trophoblast cells pump sodium ions into the center of the embryo, which causes water to enter through osmosis. This forms an internal fluid-filled cavity called the blastocoel. This distinguishable blastocoel cavity in addition to cellular specification are both hallmark identities of the blastocyst.

Implantation
Implantation is critical to the survival and development of the early embryo. It establishes a connection between the mother and the early embryo which will continue through the remainder of the pregnancy. Implantation is made possible through structural changes in both the blastocyst and endometrial wall. The zona pellucida surrounding the blastocyst breaches, referred to as hatching. This removes the constraint on the physical size of the embryonic mass and exposes the outer cells of the blastocyst to the interior of the uterus. Furthermore, hormonal changes in the mother, specifically a peak in luteinizing hormone (LH) prepares the endometrium to receive the blastocyst and envelope it. Once bound to the extracellular matrix of the endometrium, trophoblast cells secrete enzymes and other factors to embed the blastocyst into the uterine wall. The enzymes released degrade the endometrial lining, while autocrine growth factors such as human chorionic gonadotropin (hCG) and insulin-like growth factor (IGF) allow the blastocyst to further invade the endometrium.

Implantation in the uterine wall allows for the next step in embryogenesis, gastrulation, which includes formation of the placenta from trophoblastic cells and differentiation of the ICM into the amniotic sac and epiblast.

Structure
The blastocyst is made up of blastomere cells and the blastocoel.

There are two types of blastomere cells:
 * The inner cell mass, also known as the embryoblast, gives rise to the primitive endoderm and the epiblast.
 * The primitive endoderm develops into the amniotic sac which forms the fluid-filled cavity that the embryo resides in during pregnancy.
 * The epiblast gives rise to the 3 germ layers of the developing embryo during gastrulation (endoderm, mesoderm, and ectoderm).
 * The trophoblast is a layer of cells forming the outer ring of the blastocyst that combines with the maternal endometrium to form the placenta. Trophoblast cells also secrete factors to make the blastocoel.
 * Cytotrophoblast is the inner layer of the trophoblast, comprised of stem cells which give rise to cells comprising the chorionic villi, placenta, and syncytiotrophoblast.
 * Syncytiotrophoblast is the outermost layer of the trophoblast. These cells secrete proteolytic enzymes to breakdown the endometrial extracellular matrix to allow for implantation of the blastocyst in the uterine wall.

The blastocoel fluid cavity contains amino acids, growth factors, and other necessary molecules for cellular differentiation.

Cell specification
Multiple processes control cell lineage specification in the blastocyst to produce the trophoblast, epiblast, and primitive endoderm. These processes include: gene expression, cell signaling, cell-cell contact and positional relationships, and epigenetics.

Once the ICM has been established within the blastocyst, this cell mass prepares for further specification into the epiblast and primitive endoderm. This process of specification is determined in part by Fibroblast Growth Factor (FGF) signaling which generates a MAP kinase pathway to alter cellular genomes. Further segregation of blastomeres into the trophoblast and inner cell mass are regulated by the homeodomain protein, Cdx2. This transcription factor represses the expression of Oct4 and Nanog transcription factors in the trophectoderm. These genomic alterations allow for the progressive specification of both epiblast and primitive endoderm lineages at the end of the blastocyst phase of development preceding gastrulation.

Trophoblasts express integrin on their cell surfaces which allow for adhesion to the extracellular matrix of the uterine wall. This interaction allows for implantation and also triggers further specification into the 3 different cell types, preparing the blastocyst for gastrulation.

Clinical implications
Understanding of blastocyst development has important consequences in medicine and family planning, namely in pregnancy testing and in-vitro fertilization.

Pregnancy test
Levels of human chorionic gonadotropin secreted by the blastocyst during implantation is the factor measured in a pregnancy test. HCG can be measured in both the blood and urine to determine if a woman is pregnant. More hCG is secreted in a multiple pregnancy. Blood tests of hCG can also be used to check for abnormal pregnancies.

Blastocyst in vitro fertilization
Blastocysts have played a major role in the advancement of in-vitro fertilization. IVF is an alternative to traditional in vivo fertilization for fertilizing an egg with sperm and implanting that embryo into a female’s womb. For many years the embryo was inserted into the fallopian tube two to three days after fertilization. However at this stage of development it is very difficult to predict which embryos will develop best, and several embryos were typically implanted. Several implanted embryos helped to guarantee that there would be a developing fetus but it also led to the development of multiple fetuses. This was a major problem and drawback for using embryos to IVF.

A recent breakthrough in in vitro fertilization is the use of blastocysts. A blastocyst would be implanted five to six days after the eggs had been fertilized. After five or six days it is much easier to determine which embryos will result in healthy live births. Knowing which embryos will succeed allows just two or three blastocysts to be implanted, cutting down on multiple births. Now that the nutrient sources for embryonic and blastocyst development has been determined, it is much easier to give embryos the correct nutrients in order to sustain them into the blastocyst phase. Blastocyst implantation through in vitro fertilization is a painless procedure in which a catheter is inserted into the vagina, guided through the cervix via ultrasound, into the uterus where the blastocysts are inserted into the womb.

Blastocysts also offer an advantage because they can be used to genetically test the cells to check for genomic problems. There are enough cells in a blastocyst that a few cells are able to be removed without disturbing the developing blastocyst. These cells can be tested for genetic defects using immunofluorescence.

Blastocyst in art
Gustav Klimt, an artist of the early 20th Century, often depicted romantic and sexual scenes in his artwork and paintings. In 1907, Klimt undertook the task to portray the Zeus' impregnation of Danae. In the myth of Danae, daughter of the King Acrisius of Argos, it was prophesized that Acrisius would be killed by his own grandson. In order to prevent his death, the king secluded his daughter so that she would never have any children. Zeus, however tricks Danae, and impregnates her in the form of a golden shower. The son that resulted from this impregnation, Perseus, eventually does inadvertently kill Acrisius by hitting him in the head with a discus. In his masterpiece, Klimt depicts Zues as the sheets of gold and string and with a black rectangle representing Zeus’ phallic structure. Particularly intriguing in Klimt’s Danae is the shawl that enshrouds Danae. On this shawl, there are what art historians for years referred to as little golden ovaloids. However, upon further investigation these ovaliods have a striking similarity to the structure of blastocysts. This depiction carries along the theme of fertility and development associated with the Greek myth. Klimt’s portrayal of Danae curled up in the fetal position also points towards human development in the womb. The themes of sexuality, fertilization, and development are all support that Klimt intentionally meant for the ovaloids to be blastocysts. However, when Klimt painted Danae in 1907, blastocysts were not common knowledge among the public. Blastocyst had not even been looked at until August Rauber and Rudolf Leuckart described them as a diagnostic stage of mammalian development in the 1880s. Rauber was a leading biologist of the time and made great leaps in developmental biology by combining comparative biology and molecular pathways of early growth, development, and differentiation. Klimt most likely received his knowledge of the blastocyst from frequenting salons. Emil Zuckerkandl, a respected anatomist from Vienna, frequently gave lectures at the Zuckerkandl salon concerning his research. These presentations often included slide shows of his findings. Emil’s wife Berta Zuckerkandl, was the driving force behind having respected artists come to the salon along with the more typical scientists, politicians, and philosophers. This mix of professions allowed the opportunity for Klimt to see groundbreaking biological discoveries such as the blastocyst. It also would have provided an arena for Klimt to ask questions not only to Zuckerkandl, but also to the leading embryologist in Vienna, Hans Leo Przibram. Klimt thus successfully used cutting edge biological knowledge to represent the successful impregnation of Danae. This tactic was also very important because Klimt’s paintings had been under scrutiny, because his recent paintings were too explicit. This move towards using a new discovery allowed him thus to get his point across subtly so that later generations would be able to behold his masterpiece.