Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development, the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula (from Greek βλαστός (blastos meaning sprout)) is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.

A common feature of a vertebrate blastula is that it consists of a layer of blastomeres, known as the blastoderm, which surrounds the blastocoel. In mammals, the blastocyst contains an embryoblast (or inner cell mass) that will eventually give rise to the definitive structures of the fetus, and a trophoblast which goes on to form the extra-embryonic tissues.

During blastulation, a significant amount of activity occurs within the early embryo to establish cell polarity, cell specification, axis formation, and to regulate gene expression. In many animals, such as Drosophila and Xenopus, the mid blastula transition (MBT) is a crucial step in development during which the maternal mRNA is degraded and control over development is passed to the embryo. Many of the interactions between blastomeres are dependent on cadherin expression, particularly E-cadherin in mammals and EP-cadherin in amphibians.

The study of the blastula, and of cell specification has many implications in stem cell research, and assisted reproductive technology. In Xenopus, blastomeres behave as pluripotent stem cells which can migrate down several pathways, depending on cell signaling. By manipulating the cell signals during the blastula stage of development, various tissues can be formed. This potential can be instrumental in regenerative medicine for disease and injury cases. In vitro fertilisation involves the transfer of an embryo into a uterus for implantation.

The blastula stage of early embryo development begins with the appearance of the blastocoel. The origin of the blastocoel in Xenopus has been shown to be from the first cleavage furrow, which is widened and sealed with tight junctions to create a cavity.

In many organisms the development of the embryo up to this point and for the early part of the blastula stage is controlled by maternal mRNA, so called because it was produced in the egg prior to fertilization and is therefore exclusively from the mother.

In many organisms including Xenopus and Drosophila, the midblastula transition usually occurs after a particular number of cell divisions for a given species, and is defined by the ending of the synchronous cell division cycles of the early blastula development, and the lengthening of the cell cycles by the addition of the G1 and G2 phases. Prior to this transition, cleavage occurs with only the synthesis and mitosis phases of the cell cycle. The addition of the two growth phases into the cell cycle allows for the cells to increase in size, as up to this point the blastomeres undergo reductive divisions in which the overall size of the embryo does not increase, but more cells are created. This transition begins the growth in size of the organism.

The mid-blastula transition is also characterized by a marked increase in transcription of new, non-maternal mRNA transcribed from the genome of the organism. Large amounts of the maternal mRNA are destroyed at this point, either by proteins such as SMAUG in Drosophila or by microRNA. These two processes shift the control of the embryo from the maternal mRNA to the nuclei.