Week 1 begins at conception and typically occurs approximately 14 days after the onset of the last menstrual period. Embryonic age at week 1 therefore correlates with a gestational age of 3 weeks. Fertilization normally takes place in the ampulla of the fallopian tube (Fig. 2.2) [2, 3]. The sperm penetrates the corona radiata of the ovum, binds to, and then penetrates the zona pellucida. It then enters the oocyte membrane, fuses to the oocyte, and forms a highly specialized totipotent cell called the zygote [1]. After its formation, the zygote undergoes cleavage , which is characterized by a sequence of mitotic cell divisions into daughter cells called blastomeres [1, 2].

Cleavage starts approximately 30 h after fertilization. The mass of the blastomeres does not increase during these divisions, so the entire embryo maintains its size [2, 4].

Three days after fertilization the conceptus consists of 12–32 blastomeres and becomes the morula [1]. The morula enters the uterus approximately 4 days after fertilization [5]. Fluid accumulates within the morula and forms a cavity [4, 6]. At this point, the developing human is called the blastocyst . This cavity separates the conceptus into two parts (Fig. 2.2):

Approximately 4 days after fertilization, the zona pellucida degenerates. Six to seven days after fertilization (day 20 after the first day of the last menstrual period), the blastocyst attaches to the endometrium and implantation begins [1].

Implantation typically occurs at the posterior and superior portion of the uterus , in the functional layer of the endometrium during the secretory phase of the menstrual cycle. As the blastocyst attaches to the endometrium, the trophoblast will differentiate into the cytotrophoblast and the syncytiotrophoblast [7].

The process of implantation occurring during the second week can be divided into four stages: lysis or “hatching” of the surrounding zona pellucida; apposition of trophoblast cells into the decidua of endometrium; adhesion; and invasion [8]. At implantation (Fig. 2.2), the embryoblast undergoes cellular proliferation and differentiation into two layers:

These two layers form the primordial bilaminar embryonic disc, which will give rise to the three germ cell layers that will form all the body’s tissues and organs (Fig. 2.3).

Upon implantation of the blastocyst , the syncytiotrophoblast produces human chorionic gonadotropin (hCG). Secreted hCG enters the maternal blood via the lacunae, which are small blood-filled spaces that form in the syncytiotrophoblast. These lacunae will form a primitive uteroplacental circulation to pass oxygen and provide nutrients to the embryonic disc. Production of hCG is sufficient by the end of the second week to yield a positive pregnancy test [9].

Within the epiblast, small clefts develop that subsequently coalesce and form the primordium of the amniotic cavity [2]. This primordial amniotic cavity becomes lined by a thin layer of cells from the epiblast to form the amnion [10].

Hypoblast cells migrate and line the inner surface of the cytotrophoblast to form the exocoelomic membrane, which delimits the former blastocyst cavity and forms the primary umbilical vesicle.

Connective tissue from the epiblast surrounds the amnion and umbilical vesicle, filling the space between the exocoelomic membrane and the cytotrophoblast, forming the extraembryonic mesoderm .

Fluid-filled spaces then appear in the extraembryonic mesoderm. These spaces will form the extraembryonic coelom or chorionic cavity surrounding the amnion and umbilical vesicle. The remaining of mesoderm, called the connecting stalk, is the structure that maintains the embryonic attachment to the trophoblast. The extraembryonic coelom divides the extraembryonic mesoderm into somatic and splanchnic layers. The somatic mesoderm will merge with the trophoblast to form the chorionic sac.

During the third week, the bilaminar embryonic disc is converted into a trilaminar disc by gastrulation. These three germ layers will give rise to all the tissues and organs of the human body.

Gastrulation begins with the formation of the primitive streak, which is an indentation of the epiblastic surface in the caudal portion of the embryo (Fig. 2.4). From this primitive streak, epiblast cells migrate ventrally, laterally, and cranially between the epiblast and hypoblast. Subsequently, the epiblast transforms into embryonic ectoderm. Some epiblast cells also displace the hypoblast and form embryonic endoderm (Fig. 2.4). Mesenchymal cells occupy the area between ectoderm and endoderm, and form the intraembryonic mesoderm [11]. All three germ cell layers are derived from the epiblast [8]. These mesenchymal cells migrate between the ectoderm and mesoderm to form the intraembryonic mesoderm:

The notochord is the primordium of the vertebral column. The notochord induces a thickening in the embryonic ectoderm called the neural plate. A groove along the neural plate forms the neural folds (Fig. 2.4). The neural folds fuse with the neural plate to form the neural tube , which is the progenitor of the central nervous system (CNS ) [9]. The neural crest is formed between the surface ectoderm and neural tube. Mesoderm on each side of the notochord forms longitudinal columns of paraxial mesoderm that will give rise to the somites.

The heart and great vessels are formed from mesenchymal cells in the cardiogenic area. Endocardial heart tubes fuse to form the primordial heart tube . These tubes join with the formed blood vessels to form the primordial cardiovascular system [9].

During this period, the three germ layers differentiate into various tissues that will form the primordia of most of the major organs and systems of the body [2]. Exposure to teratogens during this period may cause malformations [10].

At this stage of development, the uteroplacental circulation alone is no longer sufficient to satisfy the increasing nutritional needs of the embryo. Development of the cardiovascular system to supplement nutritional needs is critical for survival.

Differential growth rates cause the flat embryo to develop curves and folds commencing on day 22. Due to the growth of the neural tube and the amnion in the median plane (craniocaudal folding), the enlarging sheet of the embryo pushes out and over the rim of the umbilical vesicle [2]. At the cranial end, the neural tube forms, the buccopharyngeal membrane (Fig. 2.4) is positioned where the mouth will develop, and the cells that will form the heart tube are positioned in what will be the future thorax. At the caudal end, the connecting stalk is in the region of the future umbilical cord, and the cloacal membrane is positioned more caudally (Fig. 2.4).