4-8 Week Development of Human Embryo - Organogenesis PDF

4-8 WEEK DEVELOPMENT OF HUMAN EMBRYO - ORGANOGENESIS Gizem SÖYLER, PhD Near East University Faculty of Medicine Department of Histology & Embryology  All major external and internal structures are established during the fourth to eighth weeks. By the end of this embryonic period, the main org...

4-8 WEEK DEVELOPMENT OF HUMAN EMBRYO - ORGANOGENESIS Gizem SÖYLER, PhD Near East University Faculty of Medicine Department of Histology & Embryology  All major external and internal structures are established during the fourth to eighth weeks. By the end of this embryonic period, the main organ systems have started to develop. As the tissues and organs form, the shape of the embryo changes, and by the end of this period, the embryo has a distinctly human appearance. Because the tissues and organs are differentiating rapidly, exposure of embryos to teratogens during this period may cause major birth defects. Teratogens are agents (such as some drugs and viruses) that produce or increase the incidence of major birth defects. Phases of Development Human development is divided into three interrelated phases: 1. Growth: Involves cell division and the production of cellular components. 2. Morphogenesis: The process where organs, body parts, and the whole body develop their shape and size. This is regulated by specific genes in a precise sequence, allowing cells to change shape, move, and interact to form tissues and organs. 3. Differentiation: Cells are organized into tissues and organs in a precise pattern, enabling them to perform specialized functions. Folding of Embryo The process of body formation in the embryo involves the folding of the flat trilaminar embryonic disc into a cylindrical shape. This folding occurs in both the median and horizontal planes due to the rapid growth of the embryo, with the sides growing slower than the long axis, leading to simultaneous cranial, caudal, and lateral folding. These folding processes transform the embryonic disc into a cylindrical embryo and establish the basic body structure. Head Fold Occurs at the beginning of the fourth week, forming the brain's primordium. The developing brain and forebrain overgrow cranially, moving over the developing heart. During this process, part of the umbilical vesicle’s endoderm is incorporated into the embryo as the foregut, which lies between the forebrain and heart. The head fold repositions the septum transversum, which later forms the central tendon of the diaphragm, and alters the arrangement of the embryonic coelom. Tail Fold Results from the growth of the distal neural tube, which forms the spinal cord. The tail region projects over the cloacal membrane, and part of the endoderm is incorporated as the hindgut. The hindgut later forms the cloaca, leading to the development of the urinary bladder and rectum. The primitive streak moves caudally, and the connecting stalk, which becomes the umbilical cord, attaches to the ventral surface. Lateral Folding Caused by the rapid growth of the spinal cord and somites, leading to the formation of right and left lateral folds. This folding creates the ventrolateral abdominal wall and incorporates part of the endoderm as the midgut, the precursor to the small intestine. The connection between the midgut and umbilical vesicle narrows, forming the omphaloenteric duct. The umbilical cord forms as the amniotic cavity expands, and the amnion becomes the epithelial covering of the cord. Germ Layer Derivatives The three germ layers (ectoderm, mesoderm, and endoderm) formed during gastrulation give rise to the primordia of all tissues and organs. The cells of each germ layer divide, migrate, aggregate, and differentiate in patterns as they form the various organ systems. The main germ layer derivatives are as follows; Ectoderm gives rise to The central nervous system; peripheral nervous system; sensory epithelia of the eyes, ears, and nose; epidermis and its appendages (hair and nails); mammary glands; pituitary gland; subcutaneous glands; enamel of the teeth. Neural crest cells; pigment cells of the dermis; muscles, connective tissues, and bones of pharyngeal arch origin; suprarenal medulla; meninges (coverings) of the brain and spinal cord. Mesoderm gives rise to connective tissue, cartilage, bone, striated and smooth muscles, heart, blood, and lymphatic vessels; kidneys; ovaries; testes; genital ducts; serous membranes lining the body cavities (pericardial, pleural, and peritoneal membranes); spleen; and cortex of the suprarenal glands. Endoderm gives rise to The epithelial lining of the digestive and respiratory tracts; parenchyma (connective tissue framework) of the tonsils; thyroid and parathyroid glands; thymus, liver, and pancreas; epithelial lining of the urinary bladder and most of the urethra; and epithelial lining of the tympanic cavity, tympanic antrum, and pharyngotympanic tube  Embryonic development is guided by genetic plans in chromosomes and is influenced by genetic and environmental factors. Developmental Control Mechanisms include tissue interactions, regulated cell migration, controlled cell proliferation, and programmed cell death (apoptosis). These mechanisms ensure the synchronized development of tissues and organs. Growth occurs through cell division (mitosis) and the production of extracellular matrices, while complexity arises from morphogenesis (the shaping of organs and tissues) and differentiation (the specialization of cells).  Development involves interactions between different tissues, known as inductions, where one tissue influences the development of another. For example, the optic vesicle induces the formation of the lens from the surface ectoderm. This interaction is essential for the proper formation of structures. Inductive processes often occur in sequence, ensuring that complex structures develop orderly. In some cases, interactions are reciprocal, with each tissue influencing the other's development. Fourth Week By the end of the fourth week of pregnancy, the embryo is about 4 mm long and has developed the foundations of most major organ systems, except for the limbs and the urogenital system, which are still in their early stages. Externally, the embryo is C-shaped, with somites (blocks of mesoderm) visible along the sides of the neural tube. The head is mostly featureless except for the rudimentary eyes, ears, and a partially broken down oropharyngeal membrane. Pharyngeal arches are prominent in the neck region. The heart and liver create noticeable bulges on the ventral body wall, while the body stalk and a spiraled tail are also prominent.  During the fourth week of embryonic development, significant changes in body form occur: 1. Somite Formation: The embryo, initially almost straight, has 4 to 12 somites, which are visible as surface elevations. These somites are associated with the formation of the neural tube, which remains open at the cranial and caudal ends (neuropores). 2. Pharyngeal Arches: By day 24, the first pharyngeal arch (mandibular arch) becomes visible, contributing to the formation of the lower jaw (mandible) and upper jaw (maxilla). By day 26, three pairs of pharyngeal arches are visible, with the cranial neuropore closing. 3. Embryo Curvature: The embryo begins to curve due to head and tail folds, giving it a C-shaped appearance by mid-week. 4. Heart Development: The heart becomes prominent, producing a ventral heart prominence and beginning to pump blood. 5. Limb Buds: By days 26-27, upper limb buds appear as small swellings on the ventrolateral body walls, followed by the appearance of lower limb buds by the end of the week. 6. Sensory Organ Primordia: Otic pits, the precursors to the internal ears, and lens placodes, the precursors to the eyes, become visible on the sides of the head. 7. Tail Formation: A prominent, tail-like caudal eminence develops. 8. Organ System Rudiments: The rudiments of many organ systems, especially the cardiovascular system, are established. By the end of the fourth week, the caudal neuropore typically closes. Fifth Week During the fifth week of embryonic development, the changes in body form are relatively minor compared to the previous week, but several key developments occur: 1. Head Growth: The head grows significantly, outpacing the growth of other body regions. This is primarily due to the rapid development of the brain and facial prominences. 2. Facial and Heart Proximity: As the face continues to develop, it moves closer to the heart prominence. 3. Pharyngeal Arch Development: The second pharyngeal arch grows rapidly and overgrows the third and fourth arches, creating a lateral depression on each side called the cervical sinus. 4. Mesonephric Ridges: The mesonephric ridges become visible, marking the location of the developing mesonephric kidneys, which serve as interim excretory organs during this stage. Sixth Week During the sixth week of embryonic development, several significant changes occur: 1. Spontaneous Movements: Embryos begin to exhibit spontaneous movements, such as twitching of the trunk and developing limbs. Reflex responses to touch have also been observed at this stage. 2. Upper Limb Differentiation: The upper limbs show regional differentiation, with the development of elbows and large hand plates. The primordia of the digits (fingers), known as digital rays, start to form in the hand plates. 3. Lower Limb Development: The lower limbs begin to develop, occurring 4 to 5 days later than the upper limbs. 4. Auricular Hillocks: Small swellings called auricular hillocks develop around the pharyngeal groove between the first two pharyngeal arches. This groove becomes the external ear canal, and the auricular hillocks contribute to forming the auricle (pinna), the shell-shaped part of the external ear. 5. Eye Development: The eyes become more prominent, largely due to the formation of retinal pigment. 6. Head and Trunk Changes: The head grows larger relative to the trunk and bends over the heart prominence due to bending in the cervical (neck) region. The trunk and neck begin to straighten. 7. Intestinal Development: The intestines enter the extraembryonic coelom in the proximal part of the umbilical cord, a normal event known as umbilical herniation, occurring because the abdominal cavity is too small to accommodate the rapidly growing intestines. Seventh Week During the seventh week of embryonic development, significant changes occur, particularly in the limbs. More defined human form occurs with the limbs and skeletal system becoming more distinct. 1. Limb Development: The limbs undergo considerable change, with notches appearing between the digital rays in both the hand and foot plates. These notches indicate the formation of digits (fingers and toes). 2. Gut and Yolk Sac Changes: Communication between the primordial gut and the umbilical vesicle is reduced, with the yolk stalk transforming into the omphaloenteric duct. 3. Bone Ossification: By the end of the seventh week, ossification (bone formation) begins in the bones of the upper limbs. Eighth Week During the eighth week of embryonic development, significant changes occur as the embryo takes on more distinct human features: 1. Limb Development: The digits of the hands are separated but initially webbed. By the end of the week, the digits have lengthened and are fully separated. The notches between the digital rays of the feet are also clearly visible. 2. Caudal Eminence: The caudal eminence is still present at the start of the week but becomes stubby and eventually disappears by the end of the week. 3. Scalp Vascular Plexus: The scalp vascular plexus forms a characteristic band around the head. 4. Limb Movements and Ossification: Purposeful limb movements begin, and primary ossification starts in the femora (thigh bones). 5. Human Characteristics: The embryo now exhibits distinct human characteristics, with a neck established and more obvious eyelids, which begin to close and fuse. However, the head remains disproportionately large, making up almost half of the embryo's total size. 6. Genitalia: There are slight sex differences in the appearance of the external genitalia, but they are not yet distinctive enough for accurate sexual identification. 7. Intestines: The intestines remain in the proximal portion of the umbilical cord. Estimation of Embryonic Age Embryonic age is often estimated based on external characteristics and length, particularly in cases of spontaneous abortion. Measurements like crown-rump length (CRL) are frequently used, especially for embryos aged 14 to 18 weeks. However, size alone may be unreliable because some embryos exhibit slower growth rates before death. Measurement Techniques Third and Early Fourth Weeks: Embryos are straight, so measurements reflect the greatest length. Crown–Rump Length (CRL): Used for older embryos; it’s assumed that the longest CRL is the most accurate. Crown–Heel Length: Sometimes measured as standing height. Length is just one criterion; the Carnegie Embryonic Staging System is used internationally for more accurate staging and comparison.  Obstetricians typically date pregnancy from the first day of the last normal menstrual period (LNMP), referred to as gestational age. Embryonic age begins at fertilization, roughly two weeks after the LNMP. For patients undergoing in vitro fertilization or artificial insemination, fertilization age is used. Knowing the exact embryonic age is crucial for clinical management, especially for procedures like chorionic villus sampling and amniocentesis. Gestational age estimation may be unreliable if based solely on menstrual history, particularly in women with variable ovulation, spotting during implantation, or after cessation of oral contraception.  The most accurate way to estimate embryonic age is by knowing the day of fertilization, typically calculated from the time of ovulation. Fertilization usually occurs within 12 hours of ovulation. Any statement about embryonic age should indicate whether it's based on days after LNMP or after the estimated time of fertilization. Factors Affecting LNMP Reliability Potential sources of error include oligomenorrhea (irregular and inconsistent menstruation), pregnancy shortly after childbirth, and use of intrauterine devices. Despite these factors, the LNMP is generally a reliable criterion for most women. Ultrasound assessments provide a more accurate estimation by measuring the size of the embryo and chorionic cavity. Ultrasound Examination of Embryos Most women seeking obstetric care have at least one ultrasound examination during their pregnancy for one or more of the following reasons: Estimation of gestational age for confirmation of clinical dating Evaluation of embryonic growth when intrauterine growth restriction is suspected Guidance during chorionic villus or amniotic fluid sampling Examination of a clinically detected pelvic mass Suspected ectopic pregnancy Detection of possible birth defects