1

2

The zygote is still not an embryo because the paternal and maternal gene pools have not yet merged.

3

Superior izquierda: The paternal and the maternal pronuclei move towards each other with the help of microtubules, which begin to be formed immediately after impregnation, i.e., by the penetration of the spermatozoon. They grow in a star-like pattern out of the paternal centrosome directly beside the forming paternal pronucleus (= formation of an aster made of dozens of microtubules). The microtubular proteins themselves arise from the cytoplasma of the oocyte. Inferior derecha: While the microtubules of the aster pull the pronuclei together in the center of the oocyte, the synthesis of the DNA is taking place in the pronuclei. This duplication takes roughly 12 hours. The pronuclei grow in size in this time.

4

Superior izquierda: After the two pronuclei have come as close together as they can, no merging of them takes place, i.e., a fitting together of the chromosomes of the two pronuclei within a single nucleic membrane does not happen. It is much more accurate to say that the nucleic membranes of both pronuclei dissolve and the chromosomes of both align themselves on the spindle apparatus at the equator. Inferior derecha: The mitotic spindle divides the chromosomes that have just been brought together into the two first cells of the embryo. This proceeding towards the two-cell stage occurs on average between 22 and 26 hours after fertilization. Video: The pronuclei are still approaching each other and thereby position themselves so they are optimally oriented for the impending division (turning of the pronucleus pair). The pronucleus membrane dissolves and thus the pronuclei are no longer recognizable. Now the zygote has been created. Following a phase of great movement the division occurs and a new nucleus forms in each cell (visible towards the end in the right cell).

5

6

On the 4th day after insemination the outermost cells of the morula that are still enclosed within the pellucid zone begin to join up with each other (so-called compaction). An epithelial cellular layer forms, thicker towards the outside, and its cells flatten out and become smaller. The cells contact one another by means of tight junctions and gap junctions. A cavity forms in the interior of the blastocyst into which fluid flows (the so-called blastocyst cavity). The two to four innermost cells of the preceding morula develop into the so-called inner cell mass of the blastocyst. The actual embryo will develop solely from these cells (embryoblast). These cells are concentrated at one pole, the embryonic pole of the blastocyst. What has thus been formed is an outer cell mass (the trophoblast), consisting of many flat cells, and the embryoblast, formed from just a few rounded cells. The ratio between the number of embryoblast cells to those making up the trophoblast amounts to roughly 1:10. From the trophoblast the infantile part of the placenta and the fetal membranes will arise.

7

Around the end of the fifth day the embryo frees itself from the enveloping pellucid zone. Through a series of expansion-contraction cycles the embryo bursts the covering. This is supported by enzymes that dissolve the pellucid zone at the abembryonic pole. The rhythmic expansions and contractions result in the embryo bulging out of and emerging from the rigid envelope. This "first birth" is called hatching.

8

After the apposition of the free blastocyst at the uterine epithelium (4) themicrovilli on the surface of the outermost trophoblast cells interact with the epithelial cells of the uterus. In this stage the blastocyst can no longer be eliminated by a simple flushing out. The adhesion of the blastocyst on the endometrium arises through cell surface glycoproteins, the specific mechanisms of which, though, are not yet well understood.

9

The cytotrophoblast, deep inside, consists in an inner irregular layer of ovoid, single- nucleus cells. This is also where intensive mitotic activity takes place.In the periphery the syncytiotrophoblast forms a syncytium, i.e., a multi-nucleic layer without cell boundaries that arises from the fusion of cytotrophoblast cells. The syncytiotrophoblast produces lytic enzymes and secretes factors that cause apoptosis of the endometrial epithelial cells. The syncytiotrophoblast also crosses the basal lamina and penetrates into the stroma that lies below, eroding the wall of capillaries. With the implantation of the blastocyst in the endometrium the syncytiotrophoblast develops quickly and will entirely surround the embryo as soon as it has completely embedded itself in the endometrium.

10

In the middle of the 2nd week extracellular vacuoles appear in the ST. They join together forming lacunae. Initially these lacunae are filled with tissue fluids and uterine secretions. Following the erosion of the maternal capillaries, their blood fills the lacunae that later develop further into intervillous spaces. The invasive growth of the ST ceases in the zona compacta of the endometrium. At around the 13th day theprimitive utero-placental circulatory system arises.

11

The development of the bilaminar germ disk 3 and the establishment of a feto-maternal blood circulation system were given in detail in the placenta andimplantation modules. In the bilaminar primordium of the embryo (hypoblast or primary endoderm and epiblast) one recognizes in the epithelium of the epiblast a fluid-filled space, the first primordium of theamniotic cavity 5. Ventrally, the roof of the still incompletely uncovered primary umbilical vesicle 5 (previously the blastocyst cavity) is formed by the hypoblast. Schematically, amniotic cavity and primary umbilical vesicle together formtwo hemispheres with two layers (epi- and hypoblast) lying close to one another, thus representing the first embryonic primordium. However, only the epiblast is responsible for forming the embryo. Thehypoblast develops into a part of the extraembryonic appendages.

12

13