BMS150 Wk 8

Meiosis and Gamete Formation

• A diploid cell (germ cell) undergoes meiosis to produce a unique haploid gamete.
• Crossing-over between maternal and paternal chromatids during prophase I results in "mixed" chromatids, containing some paternal and some maternal genes.
• Meiosis is not completed in an oocyte until the sperm penetrates the oocyte.

Fertilization and Zygote Formation

• Spermatic pronucleus and the oocyte pronucleus fuse, thus completing fertilization.
• The combination of spermatic and oocyte genetic material results in a diploid cell.
• The single diploid cell is called a zygote.

Ovulation and Fertilization

• A person with ovaries is born with a certain number of diploid oocytes that have been "paused" during the first stage of meiosis.
• After puberty, the ovaries release an ovum each cycle into the uterine tubes.
• Fertilization typically occurs in the ampulla of the uterine tube.
• The oocyte will not complete meiosis II unless fertilization occurs.

From Zygote to Blastocyst

• The embryo develops from zygote to blastocyst from days 1-5.
• Cell divisions known as cleavage occur, and cells are known as blastomeres.
• The blastocyst consists of four structures: trophoblast, embryoblast, blastocoel, and zona pellucida.
• The trophoblast develops into a syncytiotrophoblast and cytotrophoblast.

Implantation

• The blastocyst "hatches" out of the zona pellucida at day 6.
• The trophoblast of the blastocyst contacts the endometrium and adheres to it.
• Adhesion is mediated by selectin and integrin binding.
• The syncytiotrophoblast invades the endometrial stroma and forms villi.

Embryonic Development

• The inner cell mass differentiates into two distinct layers: epiblast and hypoblast.
• The epiblast will become the embryo proper.
• The hypoblast will line the blastocystic cavity and form the primary yolk sac.
• The extraembryonic coelom develops between the cytotrophoblast and the hypoblast.

Week 2

• The embryo is completely embedded within the endometrium by day 10.
• The decidual cells undergo decidualization and accumulate glycogen and lipids.
• The extraembryonic coelom becomes the chorionic cavity.

Development of Extraembryonic Structures

• The amniotic cavity, secondary umbilical vesicle, and bilaminar disk are attached to the chorion via the connecting stalk.
• The chorion consists of the extraembryonic somatic mesoderm and the trophoblast.
• The chorionic sac encloses the embryo and its cavities.

End of Week 2

• The prechordal plate appears at the end of week 2.
• The prechordal plate is an embryonic organizing centre that is responsible for the induction of other structures.
• The hypoblast is an organizer of the head and mouth region.

Week 3 - Gastrulation

• Gastrulation is the process by which the three germ layers of the embryo are established.

• The process of gastrulation begins with the formation of the primitive streak.

• The primitive streak results in the formation of the primitive node and groove.

• Cells leave the deep surface of the streak and form mesenchyme, which forms the supporting tissues of the embryo.### Embryonic Development

• Embryonic mesoderm originates from mesoblastic cells, which are undifferentiated mesoderm cells.

• During week 3, cells from the epiblast, primitive node, and primitive streak displace the hypoblast, forming the embryonic endoderm in the roof of the umbilical vesicle.

• The remaining cells in the epiblast form the embryonic ectoderm.

Mesenchyme Development

• Mesenchyme forms from mesoblastic cells, which are undifferentiated mesoderm cells.
• Mesenchymal cells derived from the primitive streak migrate widely and differentiate into diverse cell types, such as:
  • Fibroblasts
  • Chondroblasts
  • Osteoblasts

Primitive Streak Development

• The primitive streak diminishes in size and becomes an insignificant structure in the sacrococcygeal region by the end of week 4.
• The primitive streak disappears by the end of week 4.

Early Embryology Overview

• Week 1:
  • Begins with fertilization
  • Develops from a single cell to a "ball" of cells (blastocyst) with an inner cell mass, trophoblast, and blastocoel
  • Hatches from the zona pellucida
  • Adheres to the endometrium and begins implantation
  • Size: approximately 0.1 mm
• Week 2:
  • Trophoblast develops into syncytiotrophoblast and cytotrophoblast
  • Embryo "sinks" beneath the endometrium
  • Trophoblastic extensions begin to interface with maternal blood vessels
  • Embryoblast develops into a bilaminar disk (epiblast + hypoblast)
  • Size: approximately 0.2 mm
• Week 3:
  • Gastrulation: bilaminar disk becomes a trilaminar disk (three germ layers)
  • Notochord forms, followed by the development of the neural groove, neural plate, and early neural tube
  • Paraxial mesoderm and somites develop
  • Tertiary chorionic villi, heart tube, and primordial circulation develop
  • Size: approximately 0.7 mm

The Notochord

• Roles of the notochord:
  1. [To be completed]

Week 3 - Embryonic Development

• The notochord is established, giving the embryo a longitudinal axis and rigidity.
• The notochord provides signals for the development of axial musculoskeletal (MSK) structures and the central nervous system (CNS).
• The notochord contributes to the formation of intervertebral discs.

Development of the Notochord

• Mesenchymal cells migrate into the primitive pit and move cephalad, forming a cord called the notochordal process.
• The notochordal process develops a lumen known as the notochordal canal.
• The notochordal process approaches the prechordal plate, and the floor of the process fuses with the endoderm.
• The notochordal plate is formed, and the amniotic cavity and the umbilical vesicle can communicate through the neurenteric canal.
• The notochordal plate cells proliferate and fold inwards, forming the fully-developed notochord.

Transformation of the Notochordal Process

• The notochordal process transforms into the notochordal plate.
• The notochordal plate contributes to the development of the autonomic nervous system ganglia, neurolemma sheaths of peripheral nerves, arachnoid and pia mater, adrenal medulla, melanocytes, craniofacial bone and cartilage, and portions of the heart.

Intraembryonic Mesoderm

• During the 3rd week, the intraembryonic mesoderm proliferates to form a thick column of mesoderm on either side of the notochord.
• The paraxial mesoderm is formed beside the axis of the organism, and the intermediate mesoderm is found just lateral to the paraxial mesoderm.
• The lateral mesoderm is lateral to the intermediate mesoderm.

Somites

• Somites develop adjacent to the neural tube during the 3rd-5th week.
• Somites are formed from the paraxial mesoderm and give rise to most of the axial skeleton and associated musculature, as well as the dermis in those areas.

Intraembryonic Coelom

• The primordium of the intraembryonic coelom appears as isolated spaces in the lateral mesoderm and cardiogenic mesoderm.
• The spaces coalesce to form a single horseshoe-shaped intraembryonic coelom.
• The intraembryonic coelom divides the lateral mesoderm into two layers: somatic and splanchnic.

Embryonic Folding

• Embryonic folding is the process by which the embryonic disc becomes more cylindrical in shape.
• Folding occurs in two planes: median and horizontal.
• The neural tube forms from the neural groove, and the neuropores close by day 27.

Spinal Cord Development

• The neural tube develops into an inner ventricular zone, a medial intermediate zone, and an outer marginal zone.
• The ventricular zone gives rise to all neurons and macroglia.
• The intermediate zone becomes populated with primordial neuroblasts.
• The outer marginal zone develops into white matter tracts.

Brain Development

• The neural folds in the cranial region fuse and close the rostral neuropore, forming three primary brain vesicles: forebrain, midbrain, and hindbrain.
• The forebrain partially divides into two secondary brain vesicles: telencephalon and diencephalon.
• The rhombencephalon also partially divides into metencephalon and myelencephalon.

Early Fetal-Maternal Circulation

• By the end of the 2nd week, the embryo is surrounded by:
  • An amniotic cavity at the dorsal surface, lined by amnioblasts
  • Extraembryonic somatic mesoderm surrounding the amnioblasts and forming the connecting stalk
  • The umbilical vesicle at the ventral surface, which will eventually become smaller as the embryo develops and undergoes folding
  • The chorion, consisting of extraembryonic somatic mesoderm on the inside and trophoblastic cells on the outside
• The trophoblast consists of:
  • Cytotrophoblast
  • Syncytiotrophoblast, which invades the endometrial stroma and induces the apoptotic death of decidual cells, releasing energy-rich glycogen and lipids that can feed the embryo
  • Syncytiotrophoblast secretes hCG, allowing the ovary to continue secreting high levels of progesterone, preventing menstruation
• The cytotrophoblast begins to form primary chorionic villi that project into the lacuna

Maternal-Fetal Circulation

• By the 4th week, the embryo and chorion have grown large enough that diffusion of nutrients between the embryo and endometrium is inadequate
• A circulation that exchanges between the maternal and fetal tissues is necessary
• The embryonic heart begins to beat at day 21, and by that stage, blood vessels and red blood cells are present in the fetus, and gas/nutrient/electrolyte/waste exchange between the mother and embryo increases
• The maternal-fetal circulation depends on:
  • A fetal cardiovascular system
  • Structures within the endometrium that allow exchange with the fetal cardiovascular system

Chorionic Villi

• Primary chorionic villi: present in week 2, composed of cytotrophoblasts surrounded by a syncytiotrophoblastic shell
• Secondary chorionic villi: present in week 3, composed of an extraembryonic mesenchymal core surrounded by cytotrophoblastic and syncytiotrophoblastic shell
• Tertiary chorionic villi: present by the end of week 3, with blood vessels (capillaries) within the mesenchymal core, allowing fetal blood to exchange substances with the maternal lacuna through the membrane formed by the tertiary villus

Maternal-Fetal Circulation - Week 3

• Day 16: The chorionic villi develop, and the cytotrophoblast proliferates and extends through the syncytiotrophoblast layer
• Day 21: The embryonic heart begins to beat, and blood vessels and red blood cells are present in the fetus

Development of Fetal Membranes

• The decidua is the endometrium in a pregnant woman, divided into three areas:
  • Decidua basalis: forms the placenta, connected to the embryo by the umbilical cord
  • Decidua capsularis: covers the embryo, but is not part of the basalis
  • Decidua parietalis: formed by the endometrium that is not part of the embryo, far from the site of implantation
• As the embryo develops, the villi within the capsularis deteriorate, and the amniotic cavity grows larger, eventually filling the uterus and contacting the decidua parietalis

Development of the Fetal Cardiovascular System

• The fetal cardiovascular system develops from the extra-embryonic tissues that develop vascular associations with the maternal decidua
• Begins in the umbilical vesicle and neighboring connecting stalk/chorion, arising from the extra-embryonic mesoderm, starts early in the 3rd week
• Embryonic vessels develop from mesoderm about 2 days after the extra-embryonic vessels develop
• Divided into vasculogenesis and angiogenesis
  • Vasculogenesis: development of brand new blood vessels from mesoderm
  • Angiogenesis: "sprouting" of blood vessels formed by vasculogenesis, connecting blood vessels to each other

Vasculogenesis and Angiogenesis

• Angioblasts derived from mesoderm develop in specialized regions known as blood islands
• The blood islands develop lumens and become blood vessels, forming vasculogenesis
• The angioblasts also give rise to red blood cells within and outside the embryo
• Red blood cells are derived from the inner lining of the new vessels (endothelium)

Development of the Embryonic Cardiovascular System

• Vasculogenesis forms angioblastic cords, which occur in the mesenchyme during gastrulation/neurulation
• The cords form a pair of endocardial heart tubes anterior to the prechordal/oropharyngeal membrane
• The caudal head fold brings the paired heart tubes caudally, towards the umbilical vesicle
• The heart tubes then fuse at the end of the 3rd week to form a primordial heart tube
• Angiogenesis links the separate cords/blood islands together to form a linked circulatory system that allows blood flow through the embryo and the developing placenta

Skeletal Muscle Tissue

• Skeletal muscles are composed of bundles of fascicles, each fascicle containing linearly aligned muscle fibers (myofibers), which are single, multi-nucleated, elongated cells.
• Each muscle fiber is composed of many sarcomeres, arranged linearly, and is surrounded by a connective tissue sheath called the endomysium.

Connective Tissue Sheath

• The connective tissue sheath surrounding the whole muscle and extending from the tendons is called the epimysium.
• The sheath surrounding each fascicle is called a perimysium.
• The sheath surrounding each individual muscle fiber is called the endomysium.

Muscle Fibers

• Muscle fibers are large, multinucleated cells containing 1000-2000 myofibrils.
• Each myofibril is composed of many myofilaments, which are made up of contractile proteins (actin, myosin), regulatory proteins (tropomyosin, troponin), and additional accessory proteins.

Contractile Proteins - Sarcomeres

• Myofibrils are arranged into a series of sarcomeres, which form the contractile unit of skeletal muscle.
• Each sarcomere consists of interdigitating myofilaments, composed of thin filaments (made of actin) and thick filaments (made of myosin).
• The striated appearance of skeletal muscle is due to the overlapping of thick and thin filaments.

Sarcomeres - Structure

• Each sarcomere is bound by the Z-disk, where thin filaments attach.
• The M-line is at the center of the sarcomere, where myosin molecules bind.
• Thick filaments lie between and partially interdigitate with thin filaments, resulting in alternating light and dark bands.

Sarcomeres - Function

• During muscle contraction, the I band (light band) shortens, while the A band (dark band) does not change in length.

Actin

• Actin is a monomer (G-actin) that forms a polymer (F-actin) which makes up the thin filaments.
• Each G-actin monomer has a binding site for myosin.
• F-actin is the major constituent of the thin filament.

Myosin

• Myosin is arranged into thick filaments composed of many myosin units, each with a head and tail region.
• The head region forms cross-bridges that interact with adjacent actin filaments.
• Many myosin units are arranged in a staggered position into a thick filament.

Myosin Head Region

• The myosin head region has ATPase activity, an actin-binding region, and an ATP binding region.

Regulatory Proteins

• Tropomyosin is a regulatory protein that associates with actin, covering the myosin-binding site on G-actin monomers in a relaxed state.
• Troponin is another regulatory protein that associates with actin, forming a complex with three subunits: Troponin I, Troponin T, and Troponin C.
• Troponin C binds to calcium, Troponin T binds to tropomyosin, and Troponin I binds to actin and inhibits contraction.

Sarcolemma

• The plasma membrane of the muscle fiber is called the sarcolemma.
• The sarcolemma contains invaginations called transverse tubules (T-tubules), which allow the action potential to be carried deep into the muscle fiber.
• The sarcolemma and T-tubules closely associate with the sarcoplasmic reticulum (SR), which contains high concentrations of calcium.

Muscle Triad

• The junction between T-tubules and sarcoplasmic reticulum cisterna is called the muscle triad.
• The muscle triad is where the action potential signals the release of calcium from the SR.

Neuromuscular Junction

• A motor nerve axon contacts each muscle fiber near the middle of the fiber, forming a synapse called the neuromuscular junction.
• The motor nerve terminal releases acetylcholine (Ach), which binds to the nicotinic receptor on the sarcolemma, giving rise to a graded, depolarizing end-plate potential.

Action Potential Propagation

• The action potential propagates along the surface of the skeletal muscle fiber and penetrates deeper into the muscle fiber via the T-tubules.
• The action potential then signals to the sarcoplasmic reticulum, releasing calcium and triggering muscle contraction.

Excitation-Contraction (EC) Coupling

• Action potential propagation along the T-tubules activates L-type Ca2+ channels in the sarcolemma, which triggers the mechanical activation of Ryanodine receptors (RYR) on the surface of the SR terminal cisterna.
• Opening of L-type Ca2+ channels and RYR allows Ca2+ to flow down its concentration gradient into the cytosol of the muscle fiber, binding to troponin (C subunit) and exposing the binding sites for myosin.

Learn about the process of meiosis in diploid cells, including crossing-over and the formation of haploid gametes. Discover how meiosis is completed in oocytes and the role of spermatic and oocyte pronuclei in fertilization.