28.2 Embryonic Development Study Notes

General Overview of Prenatal Development

  • Gestation: The period of time required for the full development of a fetus in utero. The term is derived from the word gestaregestare, meaning "to carry" or "to bear."

  • Developmental Stages and Timelines:     

    • Pre-embryonic Stage: Defined as the first 22 weeks of prenatal development.     

    • Embryonic Stage: The developing human is referred to as an embryo during weeks 383\text{--}8 of gestation.     

    • Fetal Stage: The developing human is referred to as a fetus from the 99th week of gestation until the moment of birth.

  • Characteristics of Early Development: The pre-embryonic and embryonic stages are marked by intense cell division, migration, and differentiation. By the conclusion of the embryonic period, all organ systems are structured in rudimentary form, though they remain nonfunctional or semi-functional.

Pre-implantation Embryonic Development

  • Movement of the Conceptus: Following fertilization, the zygote and its associated membranes (collectively called the conceptus) are propelled toward the uterus. This movement is facilitated by peristalsis and the beating of cilia on the epithelial cells lining the Fallopian tube.

  • Cleavage: During the journey to the uterus, the zygote undergoes 55 or 66 rapid mitotic cell divisions.    

    • Blastomere: Each daughter cell produced by these divisions is called a blastomere (blastos=blastos = "germ," "seed," or "sprout").     

    • Volume Conservation: While cleavage increases the number of cells, it does not increase the total volume of the conceptus.

  • Morula: Approximately 33 days post-fertilization, a 1616-cell conceptus reaches the uterus. The cells are compacted into a solid mass resembling a mulberry, giving it the name morula (morula=morula = "little mulberry").

  • Blastocyst Formation: The conceptus floats freely in the uterus for several days, dividing until it reaches approximately 100100 cells. It survives by consuming uterine milk, which consists of nutritive endometrial secretions.     

    • Blastocoel: The cells organize around a fluid-filled central cavity.     

    • Blastocyst Structure: At this point, the conceptus is called a blastocyst.     

    • Inner Cell Mass: A group of internal cells fated to become the embryo.     

    • Trophoblast: The outer shell of cells (trophe=trophe = "to feed" or "to nourish") which develops into the chorionic sac and the fetal portion of the placenta.

  • Totipotency: During the inner cell mass stage, cells are totipotent, meaning they can differentiate into any cell type in the human body. This state lasts only a few days before fates are determined.

  • Hatching: As the blastocyst forms, the trophoblast secretes enzymes to degrade the zona pellucida. The conceptus then breaks free in a process called hatching to prepare for implantation.

Implantation

  • Timing: Implantation begins at the end of the first week when the blastocyst adheres to the uterine wall, signaling the end of the pre-embryonic stage.

  • Location: Typically occurs in the fundus of the uterus or on the posterior wall. If the endometrium is not ready, the blastocyst may detach.

  • Failure Rates: Between 50%75%50\%\text{--}75\% of blastocysts fail to implant and are shed during menses.

  • Mechanism of Attachment: Superficial trophoblast cells fuse to form the syncytiotrophoblast, a multinucleated body that digests endometrial cells to secure the blastocyst. In response, the uterine mucosa rebuilds to envelop the blastocyst.

  • Hormonal Control (hCG): The trophoblast secretes human chorionic gonadotropin (hCGhCG).

    • Function: Directs the corpus luteum to survive and enlarge, ensuring the continued production of progesterone and estrogen to suppress menses.     

    • Detection: hCGhCG accumulates in maternal blood and urine; levels are sufficient for a positive at-home pregnancy test just a few days after implantation is complete (by the middle of the second week).

Disorders of Embryonic Development

  • Ectopic Pregnancy: Occurs when the embryo implants outside the uterus (1%2%1\%\text{--}2\% of cases).     

    • Tubal Pregnancy: Implantation in the uterine tube, often caused by scar tissue from sexually transmitted bacterial infections. Approximately 50%50\% resolve spontaneously through bleeding and contractions.     

    • Ovarian and Abdominal Ectopic Pregnancies: The egg never leaves the ovary or is lost to the abdominal cavity. Implantation can occur in the rectouterine cavity (Douglas’ pouch), the mesentery, or the greater omentum.     

    • Treatment: The cytotoxic drug methotrexate (inhibits folic acid metabolism) is used to arrest development if caught early. Surgical repair is required if the tube ruptures.

  • Placenta Previa: Occurs in 0.5%0.5\% of pregnancies when the embryo implants in the inferior portion of the uterus, near the internal os (cervical opening).     

    • Complication: The placenta partially or completely covers the cervix as it grows, leading to antepartum hemorrhage (profuse vaginal bleeding after week 2424).

Embryonic Membranes

  • Amnion: Formed from the epiblast by the end of the second week.     

    • Amniotic Fluid: Initially a filtrate of maternal plasma. At approximately the 88th week, fetal kidneys add urine to the volume.     

    • Function: Protects against trauma and temperature changes; allows for movement and prepares the fetus for swallowing and breathing.

  • Yolk Sac: Formed from the hypoblast.     

    • Function: Provides nutrients absorbed from the trophoblast and primitive blood circulation during weeks 22 and 33.     

    • Fate: Greatly reduced by week 44 when the placenta takes over. It remains the source of blood cells and germ cells (gamete precursors).

  • Allantois: A finger-like outpocketing of the yolk sac developing in week 33.     

    • Function: Serves as a primitive excretory duct; becomes part of the urinary bladder.

    • Umbilical Cord: The stalks of the yolk sac and allantois form the outer structure of the umbilical cord.

  • Chorion: The outermost membrane that surrounds all others and forms the fetal portion of the placenta.

Gastrulation and Germ Layer Formation

  • Transition: During the third week, the two-layered disc becomes a three-layered disc, and cells transition from totipotency to multipotency.

  • Primitive Streak: An indentation along the dorsal surface of the epiblast. A node at the caudal (tail) end emits growth factors to direct cell migration.

  • Primary Germ Layers:     

    • Endoderm: The first layer formed by cells displacing the hypoblast adjacent to the yolk sac. Becomes the epithelial lining of the GI tract, liver, pancreas, and lungs.     

    • Mesoderm: The middle layer of loosely connected cells. Becomes the skeleton, muscles, connective tissue, heart, blood vessels, and kidneys.     

    • Ectoderm: Formed from the remaining epiblast cells. Becomes the central and peripheral nervous systems, sensory organs, epidermis, hair, and nails.

Development and Function of the Placenta

  • Trophic Shift: Early nutrition is provided by endometrial decidual cells. Between weeks 4124\text{--}12, the placenta takes over.

  • Structure of the Placenta:     

    • Maternal Portion: Derived from the decidua basalis of the endometrium.     

    • Fetal Portion: Formed by the chorionic membrane (syncytiotrophoblast, cytotrophoblast, and extraembryonic mesoderm).     

    • Chorionic Villi: Finger-like projections that burrow into the endometrium. Fetal mesenchymal cells differentiate into blood vessels within these villi.

  • The Umbilical Cord:     

    • Umbilical Arteries (22): Carry deoxygenated blood and wastes from the fetus to the placenta.     

    • Umbilical Vein (11): Carries nutrients and oxygen from the mother to the fetus.     

    • Wharton’s Jelly: Mucous connective tissue filling the spaces around the umbilical vessels.

  • Placental Functions:     

    • Nutrition and Digestion: Mediates diffusion of glucose, amino acids, fatty acids, vitamins, and minerals. Stores nutrients for later demand.     

    • Respiration: Mediates maternal-to-fetal O2O_2 transport and fetal-to-maternal CO2CO_2 transport.     

    • Endocrine: Secretes hCGhCG, estrogens, and progesterone; mediates transmission of maternal/fetal hormones.     

    • Excretion: Filters fetal nitrogenous wastes.

  • Transport Mechanisms:     

    • Simple Diffusion: O2O_2, CO2CO_2, and lipid-soluble substances.     

    • Facilitated Diffusion: Water-soluble glucose.    

    • Active Transport: Amino acids and iron.

  • Immunological Separation: Maternal and fetal blood do not commingle. This prevents maternal cytotoxic T cells from attacking the fetus and prevents the mother from developing antibodies against fetal antigens (e.g., Rh factor) during the first pregnancy.

  • Fetotoxic Substances: The placenta is permeable to alcohol, nicotine, barbiturates, and pathogens. Alcohol consumption leads to Fetal Alcohol Spectrum Disorders (FASDFASD), causing malformations and cognitive disorders.

Organogenesis

  • Neurulation (Week 44): Development of the central nervous system from the ectoderm.     

    • Neural Plate: Thickened neuroectodermal tissue.     

    • Neural Fold/Tube: Tissues fold upward and converge to form a tube.     

    • Notochord: A rod-shaped, mesoderm-derived structure beneath the tube; becomes the nucleuspulposusnucleus\,pulposus of intervertebral discs.     

    • Somites: Block-like structures beside the tube that differentiate into the axial skeleton, skeletal muscle, and dermis.     

    • Folate Influence: Maternal folate deficiency can cause neural tube defects like spinabifidaspina\,bifida (protruding spinal tissue) or anencephalyanencephaly (absence of brain tissue).

  • Embryonic Folding: A flat sheet of cells converts into a cylinder through lateral and end-to-end folding.     

    • Primitive Gut: A tube lined by endoderm created during folding. The embryo envelops a portion of the yolk sac.

  • Early Organ Development:     

    • Heart: Begins as a tube-like structure. Starts beating at the beginning of week 44; begins pumping blood in week 55 once the liver begins producing red blood cells.     

    • Weeks 454\text{--}5: Eye pits form, limb buds appear, and pulmonary rudiments form.     

    • Week 66: Uncontrolled limb movements; GI system loops into the umbilical cord because the abdomen is too small.     

    • Hand/Foot Development: Paddle-shaped structures develop digits through apoptosis (programmed cell death) of intervening tissues.     

    • Week 77: Facial complexity increases (nostrils, outer ears, lenses).     

    • Week 88: Head is nearly the size of the body. Main brain structures are present. Genitalia are apparent but indistinguishable. Bone ossification begins.

  • Final Embryonic Dimensions: Crown-to-rump length of approx. 3cm3\,cm (1.2in1.2\,in) and weight of approx. 8g8\,g (0.25oz0.25\,oz).