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De La Salle University

Ysabela Angela Fernandez

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embryology embryonic development germ layers biology

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These notes provide an overview of embryology concepts, focusing on the establishment of germ layers and derivatives, implantation, fetal membranes, placentation, hormonal control, and the development of the somites. This is relevant to a course on embryology at De La Salle university.

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DE LA SALLE UNIVERSITY College of Science, BS-PSYC ID 121 EMBRYOL: Embryology (Lecture) Ms. Marigold Uba EMBRYOLOGY LONG EXAM 2 NOTES ○ No distinct cel...

DE LA SALLE UNIVERSITY College of Science, BS-PSYC ID 121 EMBRYOL: Embryology (Lecture) Ms. Marigold Uba EMBRYOLOGY LONG EXAM 2 NOTES ○ No distinct cellular separation ○ Spaces: Lacunae COURSE OUTLINE: Proliferation of blood cells for forming of the placenta 1. Establishment of Germ Layers & Derivatives ○ Gives rise to the Extra Embryonic Mesoderm Formation of Placenta: Extra Embryonic Membranes 2. Neural Crest Cells ○ Membranes forming outside the embryo 3. Implantation, Fetal Membrane, and Placentation 4. Hormonal Control FIRST MODULE Establishment of Germ Layers & Their Derivatives Epiblast (splits into two) ○ Embryonic Epiblast ○ Helmet like: Amniotic ectoderm Epiblast and hypoblast formation due to delamination Hypoblast process during gastrulation ○ Expands laterally and moves downward over Movement of cells via invagination passing through the blastocoel the primitive streak Synciotrophoblast ○ Moving downwards displacing the hypoblast ○ No longer distinct cellular membranes forming the endoderm ○ Lacunae Ingressing into the cavity into the blastocoel is the embryonic mesoderm Endoderm, Mesoderm, and Ectoderm RECALL ICM ICM undergoes delamination ○ Epiblast and Hypoblast Yolk sac is derived from components of hypoblast ○ Epiblast will also undergo delamination Primitive node Bilaminar Disc Formation ○ Site of invaginating cells ○ Formation of Epiblast and Hypoblast Migrating Pre notochordal cells cephalically passing Trilaminar Disk Formation primitive node ○ Formation of the 3 Embryonic Germ Layers TROPHOBLAST Cytotrophoblast ○ Contains original cells of the trophoblast, with increased population ○ Highly cellular ○ Layer of trophoblast that is responsible for the initial attachment of blastocyst to uterine lining → Uterine Wall Syncytiotrophoblast ○ It has lost cellular membranes ○ Continuous layer ○ secretes enzymatic enzymes that break uterine wall for implantation of embryo YSABELA ANGELA FERNANDEZ 1 Paraxial Mesoderm means sides of axial mesoderm ○ Also known as epimere Lateral plate Mesoderm splits into 2 ○ Parietal Mesoderm ○ Visceral Mesoderm Paraxial Mesoderm → Future Somites Intermediate Mesoderm → Future Urogenital Units Lateral Plate Mesoderm Some cells migrate downward at the hypoblast and ○ → Somatic/Parietal Mesoderm displace the hypoblast to the side to form the yolk ○ → Splanchnic/Visceral Mesoderm sac Hyopblastic layer will be replaced by forming mesodermal cells DEVELOPMENT OF SOMITE Mesoderm ○ Ingressing cells to fill in the cavity Ectoderm Epithelization of cells around a cavity ○ Cells left at the top: ○ Transformation of embryonic cells to flat cells Endoderm that are tightly packed ○ Cells displacing hypoblast: Cells loose epithelial arrangement; cells migrate Notochord deriving from pre-notochordal cells; of around neural tube and notochords as the mesodermal origin sclerotome ○ Epithelial → mesenchymal transition ○ To mesenchymal type, which can migrate FORMATION OF NOTOCHORD (CRANIAL TO CAUDAL) Dorsomedial and ventrolateral cells will form the Sagittal Section = Side View myotome Prenotochordal cells migrate through the primitive Cells that remain between the Dorsomedial and streak moving cranially Ventrolateral cells will form the dermatome Layers of Somites Cross Section: Level of Notochordal Plate ○ Sclerotome become intercalated in the endoderm to form the innermost notochordal plate around the neural tube and Stays at the midline notochord skeleton (bones) ○ Myotome Middle Layer Muscles ○ Dermatome Outermost Layer Definitive notochord Connective Tissue Finally, it detaches to form the definitive notochord Flanked on the side by intraembryonic mesoderm EXPRESSION OF GENES IN SOMITE Detached from lateral endoderm DIFFERENTIATION Formation of notochord, cranial to caudal, formed first at the cephalic region and then to the caudal region Shh and noggin expressed by the notochord and floor plate of NT→ form sclerotome FORMATION OF THREE MESODERMAL SHEETS Scleretome express PAX1 gene → controls chondrogenesis and vertebrae formation ○ Scleretome participates in the formation of vertebral column WNT proteins secreted by dorsal NT activate PAX3 gene → demarcate the dermomyotome ○ Cells that give rise to the dermis and Paraxial Mesoderm muscles Intermediate Mesoderm WNT proteins also direct dorsomedial portion of Lateral Plate Mesoderm somite → differentiate into muscle cell precursors ○ Muscle cells precursors express MYF5 Definitive notochord (muscle specific gene) ○ Mesoderm at the sides NT3 expressed by dorsal Neural Tube → middorsal It expands further to the sides to form the lateral portion of somite → dermis plate mesoderm ○ hypomere WNT protein and BNMP4 activates MyoD expression In between Lateral Plate and Paraxial is the ○ Muscle specific gene Intermediate Mesoderm ○ mesomere ENDODERM FORMATION YSABELA ANGELA FERNANDEZ 2 Originating from Endoderm: 4 Pharyngeal Pouches Cephalocaudal folding Midsagittal sections of embryos at various stages of development showing cephalocaudal foldings and its Pharyngeal Arches or Branchial Arches effects upon positions of the ○ Contain respective Aortic Arches ○ Heart Pharyngeal Folds or Gill Slits ○ Septum transversum Pharyngeal Pouch lining the gut ○ Yolk sac amnion GERM LAYER TRACING ENDODERM Digestive and Respiratory System Pharynx or foregut ○ Will give rise to pharyngeal pouches ○ Thyroid ECTODERM Nervous System, Integumentary System, and Sensory Structures Epidermal Placodes are in charge of the sensory As folding proceeds, the opening of the gut tube into vesicles the yolk sac narrows until it forms a connection Stomodeum ○ The vitelline duct ○ Anteriorly Between midgut and yolk sac ○ Rathke’s Pocket will form at the floor ○ Houses vitelline blood vessels Proctodeum ○ Lining the end part of the gut ○ Posteriorly Neural Tube ○ Central Nervous System Epiphysis Infundibulum ○ Floor of the diencephalon Infundibulum and Rathke’s Pocket ○ Pituitary gland Neural Crest Cells ○ Different ganglia Region of mesonephros showing the 2 layers of the ○ Sympathetic and parasympathetic lateral plate mesoderm Adrenal Glands ○ somatic/parietal mesoderm ○ splanchnic/visceral mesoderm MESODERM Splanchnic/Visceral Mesoderm forms linings around body cavities Lateral plate Mesoderm or Hypomere ○ Give rise to various visceral organs of the ○ Somatic Mesoderm, lining of body cavities body ○ Circulatory System Intraembryonic Cavity is formed when it splits Intermediate Mesoderm ○ Urogenital system ○ Excretory ○ reproductive system Paraxial Mesoderm ○ Skeletal system ○ Muscular System ○ Components of Integumentary System Angiogenic Clusters Mesonephric Ducts ○ For males Mullerian Ducts ○ For Females ○ These degenerate for males Muscular System Components of endodermal layers ○ Paraxial Mesoderm Digestive gut running from stomodeum to proctodeum ○ Lateral Plate Mesoderm (visceral) or cloaca Outpocketing of the digestive gut Sporadically Distributed ○ Liver ○ Endocrine System ○ Gallbladder ○ Adrenal and Pituitary Glands ○ Pancreas Vitelline Duct to Yolk Sac ○ Outpocketing the Allantois YSABELA ANGELA FERNANDEZ 3 SECOND MODULE Migrating downwards following different routes to their target routes/organs Neural Crest Cells Differentiation via cell-to-cell signaling Derived from the brim of the neuroectoderm/neural crest cells during the process of neurulation Indicative of topographical location and origin Pathway 1 ○ NCCs travel ventrally through the anterior Migrate away from the neural tube before it fully sclerotome closes Dermamayotome NCCs are Pluripotent Cells Myotome ○ Giving birth to various cell types ○ Get lodged in the anterior sclerotome of the Migratory cells from neuroectoderm somite ○ Loosely arranged ○ NCCs that will participate in the formation of ○ Amoboied movement cartilages and bones of the vertebral Undergo Epithelial-Mesenchymal Transition column ○ When giving rise to different cell types ○ No NCCs in the Posterior Sclerotome Pathway 2 NCC migratory cells to the cranial region form the ○ Take a dorsolateral route components of the face and neck: ○ Under the epidermis, above the ○ facial bones dermomyotome ○ Facial cartilages ○ Form the pigment cells in the body ○ and facial connective tissues Form pigment cells of the skin: melanocytes FOUR OVERLAPPING DOMAINS Adrenal Medulla Sensory Ganglia ○ Sympathetic Ganglia Cranial ○ Parasympathetic Ganglia ○ Pigment Cells ○ Sensory ganglia ○ Parasympathetic ganglia WHAT BECOMES OF NCCs? ○ Hormone-producing cells ○ Glia cells Neural Crest Migration Pathway Route They Follow Vagal Cell Signaling Factors in their Microenvironment of Trunk Final Destination Lumbosacral Between Vagal and Cranial MIGRATORY PATHWAYS ○ Cardiac Neural Crest Cells Lateral migration pathway ○ Fill up the innermost layer of the aortic arch ○ Form the melanocytes arteries Medial migration pathway ○ Layer that lines the lumen of arteries ○ Form the ganglia Endothelium Cranial NCC → Pharyngeal arches, face and neck Cardiac NCC (Somites 1-3) → septum between PA and Aorta Trunk NCC (Somites 6 to tail) → parasympathetic neurons Vagal NCC (Somites 1-7) Sacral NCC (Posterior to Somite 28) ○ → parasympathetic nerves of the gut Somites 18-24 → Adrenal Medulla Cardiac Neural Crest Cells ○ From Neural Tube downward to the developing Embryonic Heart Forming septum Target organs ○ Colonized by Cardiac Neural Crest Cells ○ Final locations where NCCs settle YSABELA ANGELA FERNANDEZ 4 Cardiac Neural Crest Cells line Cardiac Arteries MIGRATORY PATHS OF NCC IN HEAD REGION NCC leaves the crests of the neural folds prior to the neural tube closer Migrate to form the structures in the ○ Neck and face ○ Pharyngeal arches (1-6) ○ Epibranchial placodes (V, VII, IX, and X) Neurons and Ganglia FGF: Fibroblast Growth Factor Timing of activation of SNAIL gene is almost simultaneous with the closing of the neural tube SNAIL and FOXD3: specify cells as NCCs SLUG: promotes NCC migration from neuroectoderm Timing is almost simultaneous ○ As neural tube closes; ○ SLUG gene activates for migration of NCCs HOW IS MIGRATION INITIATED? CRANIAL NCC FROM RHOMBOMERE REGIONS Depending on what level of rhombomere they are coming from ○ Also called 4th germ layer Rhombomeres 1&2 migrate → 1st pharyngeal arch ○ Jawbones ○ Ear bones (Malleus and Incus) ○ Frontonasal process Rhombomere 4 migrate → 2nd pharnygeal arch ○ Hyoid cartilage Rhombomeres 6 migrate → 3rd and 4th Pharyngeal 1. BMP 4&7 Induce → RhoB & Slug genes (protein arch and Pouches products) ○ Thymus a. Establish cytoskeletal conditions that ○ Parathyroid gland promote migration ○ Thyroid b. Activate factors that dissociate the tight Rhombomeres 3 and 5 do not migrate through the junction in between the cells surrounding mesoderm → stay on either side of the 2. Loss of cell adhesion molecules, they are now free to rhombomere mesoderm move via amoeboid movement Neural Plate Formation ○ Concentration of BMPs (Bone HOW DO MIGRATORY AGENTS KNOW THE ROUTE ON Morphogenetic Protein) in the junctional WHICH TO TRAVEL? border of surface ectoderm neural plate 1. Path of NCC is controlled by the extracellular matrix ○ Different concentrations a. Proteins that give contact guidance/promote ○ High Level → induces epidermis formation migrations ○ Intermediate level → induces neural crest Substrate Adhesion Molecules cell formation (SAMs) ○ Low Level → Induces neural ectoderm Fibronectin, laminin, formation tenascin, collagen molecules, proteoglycans REGULATION OF NCC INDUCTION b. Proteins that restrict migrations Ephrin Proteins in the posterior sclerotome YSABELA ANGELA FERNANDEZ 5 ○ They exist in clusters of similar genes in the genome Hox genes are evolutionarily conserved from invertebrates to vertebrates Colored boxes are the clusters Paralogous chromosomes ○ A1, and B1, C1 ○ A2, B2 ○ Similar on the sides (para=side) Genes found within the same cluster ○ Orthology 2. Chemotactic and maintenance factors ○ A1, A2, A3…. a. Same in the microenvironment of the final 5’ to 3’ location of NCCs that will influence their final ○ Position of Hox Gene on the Chromosome differentiation ○ Cephalic to Caudal Region b. Soluble factors secreted by potential ○ Moves destinations The first genes to be expressed are in the anterior Ex. stem cell factors (allow side continuously proliferation of NCC) HoxA is in Chrosome 6 HoxB in Chromosome 11 FINAL DIFFERENTIATION OF TRUNK NCC HoxC in Chromosome 15 Determined by the environment into which they HoxD in Chromosome 2 migrate and settle ○ Cell signaling factors THIRD MODULE TGF-β superfamily Transformation Growth Extraembryonic Membranes Factor BMP Growth factors FGF Examples ○ BMP2 (secreted by the lungs, heart, dorsal aorta): NCC differentiates → cholinergic neurons → sympathetic ganglia in the regions ○ Endothelin-3 NCC → Melanocytes NCC → Adrenergic neurons in the gut ○ Glucocorticoids (Somite 18-24): NCC → adrenalmedullary cells ○ FGF: NCC → sympathetic neurons Formation of placenta in mammals 4 types WHAT SPECIFY THE FATES OF NCC? ○ Amnion Hox genes code for Homeodomains ○ Chorion ○ Highest hierarchy of genes ○ Allantois Control the activity of other genes ○ Yolk sac below them ○ Modify body plan DEVELOPMENT OF EXTRAEMBRYONIC MEMBRANES Combination of Hox genes ○ The genes that specify A-P axis) Hox genes have the task of organising the body plan Distinction between embryonic and extraembryonic of an animal tissues Hox genes are a particular subfamily of homeobox Scoop it up from the yolk mass that contains genes that evolved together with a Formation of Body Folds complex multicellular body plan ○ Head Folds They are utilized to convey positional information and Cephalic organize the body plan ○ Lateral Folds 3 feautures of Hox genes Sides ○ They contain a sub-class of highly conserved ○ Tail Folds homeobox sequences, so they encode Caudal transcription factors ○ They are involved in organizing body plan ICM where Primitive Streak is Formation of germ layers YSABELA ANGELA FERNANDEZ 6 ○ Endodermal cells move downward 1. Amnion occupying yolk mass 2. Chorion ○ Mesoderm move outward from the region of ○ Encompasses all the other 3 membranes the embryo to become extraembryonic 3. Allantois mesoderm 4. Yolk Sac ○ The ectoderm spreads outside away from the region of the embryo Develop a hood or helmet above the embryo the amnion Amniochorionic Fold Amnion ○ Ectoderm as innermost ○ Mesoderm as outermost ○ Forming a hood over the embryo Chorion ○ Outermost layer Oviparous Development ○ Ectoderm as outermost ○ Development outside the parent/mother ○ Extramebryonic mesoderm as innermost ○ Avian Amnion and Chorion are somatopleuric in origin ○ Plenty of yolk Yolk Sac Viviparous Development ○ Endoderm as innermost layer ○ Development inside the mother ○ Extraembryonic mesoderm as outer layer ○ Mammalian ○ In line with midgut ○ Yolk sac is vestigial, evolutionarily conserved Allantois ○ Allantois is not showed, integrated in the ○ Outpocketing of hindgut umbilical cord ○ Lined with endoderm ○ Outside with extraembryonic mesoderm Yolk Sac and Allantois and splanchnopleuric in YOLK SAC origin First membrane to make its appearance Grows over the yolk mass Functions ○ Change yolk into soluble materials for the embryo via the open midgut passing through yolk stalk ○ Endodermal cell lining as site of synthesis of serum proteins ○ Site of hematopoiesis Generation of blood cells and blood vessels ○ Site of Primordial germ Cell Specification (PGCs) AMNION Encloses the embryo in a fluid-filled cavity (amniotic cavity) ○ Most intimate with the embryo amniotic fluid Function ○ Fluid content protects the embryo from adhesions and mechanical stress CHORION In chick ○ Transport Ca2+ egg shell into the embryonic circulation → beak & skeleton ○ Exchange of respiratory gases In Mammals ○ Respiration filtration, hormone production ○ Hormone production it forms a large part of the placenta ALLANTOIS Evagination from ventral wall of hindgut Its mesoderm fused with the chorion and to some extreme with amnion Functions 4 SETS OF ExEM YSABELA ANGELA FERNANDEZ 7 ○ Chorioallantoic membrane as an efficient respiratory structure Once fused with the Chorion ○ Reservoir for excretory wastes Birds and reptiles: sequester nitrogenous wastes Hard white in the Balut Humans: contribute to the vascular network of the placenta DECIDUOUS PLACENTA At the time of parturition, the uterine tissues are Epiblast delaminates to form the amnionic ectoderm damaged and shed off; bleeding occurs Amnion separates the ICM from the trophoblast Villi are embedded within the endometrium Intimate contact Inner layer endoderm Outer layer of mesoderm NON-DECIDUOUS PLACENTA At the time of parturition, the uterine tissues are not Formation of Allantois and Chorion damaged nor shed off Villi are not embedded within the endometrium Chorion is a combination is a combination of the Loose contact extraembryonic mesoderm and the trophoblast No bleeding occurs (cytotrophoblast) Outpocketing of the hindgut Types of Placenta ○ Lined with endoderm and extraembryonic Based on shape and distribution of placental villi on mesoderm the chorionic sack enclosing the fetus Chorion in Placental Mammals ○ Diffuse ○ Mesoderm + Trophoblast ○ Cotyledonary ○ Zonary ○ Discoidal Is allantois the same as the umbilical cord? Chrorion will form a connective stalk with the maternal placenta DIFFUSE ○ This connective stalk houses the blood Greater part of chorion surface associated with vessels (arteries and veins) and allantois endometrium; the villi are spread-out The connecting stalk with blood vessels and allantois ○ Pig will be wrapped with the amnion ○ yolk sac stalk and the connecting stalk COTYLEDONARY wrapped by the amnion is the umbilical cord Contact is restricted to the localized patches of villi called cotyledons Placenta ○ Ruminants: sheep, cow, and deer ZONARY Contact involving girdlike band encircling the blastocyst; the villi are arranged in transverse zones and penetrate the uterine wall ○ Carnivores, cats, dogs DISCOIDAL Contact is restricted to a disc or plate; the villi form a disc that is intimately connected to the uterine wall ○ Humans, some rodents, rabbits Site of physiological exchange between mother and embryo ○ Made up of maternal tissue contribution and embryonic tissue contribution Types of Placenta Based on the degree of contact of placental components ○ Non deciduous placenta Types of Placenta ○ Deciduous placenta Based on histology According to the number of layers of cells separating fetal circulation from maternal circulation YSABELA ANGELA FERNANDEZ 8 Epitheliochorial is the most primitive and superficial Types of Placenta Hemochorial is the most invasive type ○ Direct connection of blood to fetal Based on the architecture of the chorionic membrane component in contact with maternal tissues Endometrial is an unusual type FOLDED Ex. swine Chorionic folds line the wrinkled surface of uterine epithelium VILLOUS Ex. primates, ruminants Chorion develops into villa (1°, 2°, 3°) ○ Primary ○ Secondary ○ Tertiary Formation of finger-like projections depending on the branches LABYRINTHINE Rodents Feto-maternal space (labyrinth) forms a network (merging of the chorionic villi surrounding maternal blood lacunae) TISSUE BARRIERS Mesh-work Point of exchange is the placenta Basal Zone, Decidual Zone Fetal Blood Vessel, Maternal Blood Vessel Maternal Components (going down) ○ Fetal nucleated, maternal non-nucleated 1. Maternal Endothelium 2. Endometrial Connective Tissue 3. Uterine Epithelium Formation of Placental Complex Fetal Components (going up) 4. Chorionic Epithelium 5. Chorionic connective tissue 6. Fetal Endothelium YSABELA ANGELA FERNANDEZ 9 Decidual ○ Components of maternal tissues that are shed off Implantation Fertilization takes place in the Ampulla of the COMPARATIVE GESTATION Oviduct ○ Travels down to the uterus Day 5 ○ It is already in the uterus ○ Blastocyst stage ICM and Trophoblast Day 7 - 10 ○ Implantation in the lining of the Uterus Earliest stage for implantation is for rabbit and swine Latest is the horse (organogenesis stage) 3 layers of the Uterus Definitive placentation is in 90 days (3 months; first ○ Endometrium trimester) ○ Myometrium ○ Perimetrium Differentiation of Trophoblast Involved in the formation of the placenta MOLECULES IN THE FORMATION OF PLACENTA cAMP & hCG ○ Direct cytotrophoblast differentiation towards a hormonally-active syncytiotrophoblast phenotype cAMP & hCG ○ Cyclic adenosine monophosphate ○ Human chorionic gonadotropin ○ Secreted when the embryo is already in the vicinity of the uterus LIF ○ Leukemia inhibitory factor TGFᵝ Cytotrophoblast LIF and TGFᵝ ○ Highly cellular ○ Downregulate the hCG synthesis and Syncitiorphoblast upregulate TUN secretion ○ Cellular boundaries are lost TUN ○ Vacuoles and fusion of vacuoles forming ○ Tropho utero nectin spaces called lacuna or lacunae ○ A part of fibronectin (substrate adhesion molecule) ○ Mediate thes the attachment of the placenta to the uterus ○ Secreted at the anchoring site YSABELA ANGELA FERNANDEZ 10 Chorion gives rise to the villa ○ Chorionic villa Chorionic plate ○ Extraembryonic mesoderm Villous capillaries will start to invade intraembryonic villi of chorion fusing with the allantoic duct Body Stalk ○ Allantoic duct ○ Invading villous capillaries Formation of Chorionic Villi Umbilical Cord ○ Umbilical Arteries and Veins Previllous embryo ○ Allantoic Duct ○ Contains mesenchymal cells Urinary Primary Villi 2nd week ○ Yolk Sac Duct ○ Mesodermal core Secondary to Tertiary Villa 3rd week ○ Branching out from primary villi ○ Core will have formation of villous capillaries ExEm of Chorion enveloping allantoid duct, yolk sac duct, villous capillaries ○ All enclosed as the umbilical cord Umbilical Cord Center has the umbilical arteries ○ Originating from the villous capillaries The Allantoic Duct/Allantois will form the urinary bladder Yolk sac will be vestigial HUMAN EMBRYONIC DISC AT 3 WEEKS Chorionic Villi to Maternal Blood in Uterus Maternal surface = Decidual cells Fetal Cell = Chorionic cells/vesicle Supply of blood from the mother is via the developing spiral arteries unloading into the intervillous spaces Pressure is high thus facilitating the blood and nutrients Pressure decreases, blood goes back to the mother passing through the maternal vein Site of exchange: placenta YSABELA ANGELA FERNANDEZ 11 Side with no villi Capsularis and parietalis fuse together will result into Umbilical cord contains the gradual disappearance of uterine cavity ○ Umbilical arteries and veins ○ Wharton’s jelly (mesenchyme cells) Chorionic Tissue Decidual Reaction LAVAE transformation of the stromal cells of the endometrium Smooth area of chorion Decidium Lacks villi; middle ply of amniotic sac ○ Tissues shed at birth ○ Extraembryonic tissues + superficial layers FRONDOSUM of endometrial connective tissue and Fetal portion of placenta epithelium Develops in the placenta Depending on its relationship with the embryo DECIDUA BASALIS (SEROTINA) Maternal placenta Where the implantation takes place and the basal plate is formed Lies between the chorionic vesicle and the uterine wall Endometrium of pregnancy beneath chorionic sac Supplies maternal blood to placenta DECIDUA CAPSULARIS (REFLEXA) Forms a capsule around the chorionic vesicle Superficial part of endometrium of pregnancy DECIDUA PARIETALIS (VERA) The remaining decidua consists of decidualized Figure 1: Blastocyst endometrium on the sides of the uterus not immediately occupied by the embryo Non-implantation area of the uterus Potential but unused site of implantation Outer ply of amnion By 4-5 days after fertilization the embryo differentiates into two distinct cell types: ○ Inner Cells Mass Develop into the fetus ○ Trophoblast Will develop into the placenta and external membranes YSABELA ANGELA FERNANDEZ 12 By this stage, the trophoblast cells have begun to Day 12 Implantation Site make the hallmark hormone ○ Human Chorionic Gonadotropin (hCG) Blastocyst completely embedded into endometrial the hormone of pregnancy-test fame stroma ↓ The invading trophoblasts have penetrated the Implantation maternal capillaries (sinusoids) ↓ Form pools of maternal blood which surround the growing trophoblasts Floating blastocyst → become attached to the uterine lining (endometrium) 3 Weeks Implantation Site (21 Days) ↓ All lacunae filled up with maternal blood via spiral Blastocyst is first slowed down by lone molecules arteries (mucins) that extend from the endometrium The embryo has already began to make an early ↓ circulatory system Cascade of molecules bring the trophoblasts into ○ All lacunae filled via spiral arteries closer contact with the endometrium ↓ ↓ Embryonic tissue and maternal blood separated by a Intimate contact is made → trophoblasts cells invade layer of cytotrophoblasts and syncytiotrophoblasts the endometrium (process of plantation) 4 Weeks Implantation Site (1 Month) Day 9 Implantation Site The basic structure of the placenta has been formed Spiral arteries are seen With maternal blood being delivered to the forming placenta via spiral arteries while being drained away via uterine veins The developing chorionic villi remain immersed in a space filled with the nutrient rich maternal blood Embryo surrounded by two layers of trophoblast ○ Inner mononuclear cytotrophoblasts ○ Outer multinucleated syncytiotrophoblast Vacuoles form → fused lacunar (lacunar stage) This arrangement of embryo, trophoblasts, and maternal tissues remains the paradigm throughout gestation Trophoblasts interface serves as ○ The means to extract nutrients from the mother ○ Protects the embryo and fetus from maternal immunological attack YSABELA ANGELA FERNANDEZ 13 Point of exchange is the placenta at the intervillous IDENTICAL TWINS spaces Fetuses are one of the same sex; Share one placenta One outer membrane envelopes both amniotic sac has the same decidual basalis FRATERNAL TWINS Fetuses may be of different sex; two placentas Two separate amniotic sacs, each with its own membrane Fraternal has different decidual basalis Functions of Placenta 1. Physiological site of maternal-fetal exchange a. Fetal maternal blood mixing Passive diffusion of blood gasses, oxygen co2 and nitrogen b. Facilitated diffusion of monosaccharides/glucose Main energy source; fetal glycemia is directly correlated with maternal glycemia Placenta & Membranes in Multiple Pregnancies c. Active transfer of amino acids Types of Twinning Diffusion of urea, ethanol 2. Works as endocrine gland; Hormone synthesis a. The syncytiotrophoblast cells of the placenta secrete four main kinds of hormones Estrogen Progesterone Two hormonal peculiar to the placenta hPL and hCG 3. Immunological Barrier a. Two important roles in fetal-maternal immunological balance Passive immunity Immunosuppression, suppression of the mother’s immune response against the fetus b. Most of the antibodies needed by the baby are acquired from the mother directly ESTROGEN During pregnancy ○ Stimulates the growth of the uterus ○ Enhances the blood flow between the uterus and the placenta ○ Causes the breast to enlarge as a preparation for milk production During baby delivery the placenta produces Progesterone and Estrogen HPL Human placental lactogen Influences growth, lactation, lipid and carbohydrate metabolism Side Notes The cytotrophoblast-the stem cell of the placenta-gives rise to the differentiated forms of trophoblasts Within the chorionic villi, cytotrophoblasts fuse to form the overlying syncytiotrophoblast The villous syncytiotrophoblast makes the majority of the placental hormones, the most studied being hCG Cyclin AMP and its analogs, and more recently hCG itself, have been sown to direct cytotrophoblast YSABELA ANGELA FERNANDEZ 14 differentiation towards a hormonally active ○ Period of sexual activity syncytiotrophoblast phenotype ○ The only time the condition of the vagina permits mating FOURTH MODULE “Period of heat” Stages (changes in the uterus, ovary, and vagina) HORMONAL CONTROL OF REPRODUCTION ○ Proestrus Period of preparation (follicles grow) Vertebrate Reproduction ○ Estrus Cyclic activity (often related to changing seasons) When mating occurs Hormonal control are regulated by environmental Corresponds with the time of cues ovulation ○ Day length Within the time range of ovulation ○ Seasonal temperature ○ Metestrus ○ Amount of rainfall Formation of corpus luteum ○ Lunar cycles Period of repair Female shifts have a cycle that lasts from 15-17 days ○ Diestrus which means that ovulation can occur on the 7th, 8th, Becomes small and anemic or 9th day Frequency of the estrous cycle during the breeding It starts summer season varies ○ Those days day length is decreasing ○ Monestrous ○ With decreasing day length, ovulatory surges Single estrous cycle in a breeding start season They end in winter Dogs and foxes ○ Season when day length is increasing ○ Polyestrous Gestation period is about 5 months Recurrence of estrous cycle in a ○ If mating is successful in October or late breeding season September, the following months until Mice, rabbits, squirrels January ○ Birth will be on February or March Their gonadal steroids and their control Spring is the most optimal time for birth ○ Ovaries Palolo worms Estrogen ○ Testes Testosterone RECALL MENSTRUAL CYCLE Anthropoid primates ○ Including humans Refers specifically to the changes that occur in the uterus ○ Uterine cycle It is caused by cyclic events that occur in the ovaries (ovarian cycle) Hypothalamus secretes and synthesizes gonadotropin releasing hormones via the portal vessels ○ Transported in the pituitary gland Gonadotropin hormones are FSH and LH ○ Follicle Stimulating Hormone ○ Luteinizing Hormone Gonads ○ Estrogen and Testosterone CYCLIC REPRODUCTIVE PATTERNS OF MAMMALS HORMONAL REGULATION FOR MALES Two types ESTROUS CYCLE Lower vertebrates Associated with more pronounced behavior cycles than are menstrual cycles Estrus YSABELA ANGELA FERNANDEZ 15 Secondary sex characteristics ○ The physical and behavioral characteristics HORMONAL REGULATION FOR FEMALES First bracket is the ovarian cycle The second bracket is the uterine cycle ○ Histological changes in the endometrium of uterus The length of the menstrual cycle on average is 28 days Ovulation is in the middle of this cycle (14th day) OVARIAN CYCLE Follicular phase (Day 1-14) ○ Day 1 of the cycle to the middle of the cycle (14th day) ○ FSH produced by the pituitary gland stimulates the growth of the follicles/granulosa cells surrounding the oocyte ○ Towards the middle, only 1 of them go into full maturation That one will be fertilized Androgens via aromatase ○ FSH and LH are released Granulosa cells secrete additional estrogen Ovulation (around Day 14) ○ Building up of estrogen secretion ○ Release of mature egg ○ Triggered by a surge in LH FOURTH MODULE An increase in estrogen from the dominant follicle causes rapid surge HORMONAL CONTROL OF REPRODUCTION in LH ○ LH surge prompts the mature follicle to release egg Luteal Phase ○ 15th-28th day ○ Ruptured follicle transforms into corpus luteum Transient endocrine structure This will cause it to produce progesterone primarily and estrogen ○ Increase in the level of Estrogen = thicken uterine lining (endometrium) ○ More granulosa cells = greater estrogen levels YSABELA ANGELA FERNANDEZ 16 ○ It sends a feedback regulation to the consists of three main phases: the follicular phase, ovulation, hypothalamus and pituitary gland and the luteal phase. These phases are regulated by various It stimulates further release in FSH hormones and take place roughly over a 28-day cycle, and LH although the length can vary from person to person. ○ LH is tagged as the hormone for ovulation A steep increase in LH causes the 1. Follicular Phase (Days 1-14) release of the mature oocyte from ○ Overview: The follicular phase begins on the the ovary first day of menstruation and ends with ○ Theca interna and the externa collapse ovulation. During this phase, the follicles Yellow body remains called the (tiny sacs containing immature eggs) in the corpus luteum ovaries start to mature, with one eventually ○ Decline at the end becoming dominant. Will send a feedback regulation at ○ Hormones Involved: the hypothalamus and pituitary Follicle-Stimulating Hormone gland (FSH): Produced by the pituitary Will generate a new batch of gland, FSH stimulates several granulosa cells follicles in the ovary to grow. WHAT IS HAPPENING IN THE UTERUS? Estrogen: As the follicles develop, they produce increasing amounts of Corresponds to Follicular Phase estrogen. Rising estrogen levels ○ Menstrual phase help thicken the uterine lining ○ Proliferative Phase (endometrium) in preparation for a With increasing level of estrogen, the uterine lining is potential pregnancy. being prepared ○ Process ○ Undergoing growth and thickening Multiple follicles begin to develop, ○ Proliferation of endometrial cells, blood but only one (or sometimes more) vessels, and endocrine glands becomes dominant, continuing to Luteal Phase grow while others regress. ○ Secretory Phase As the dominant follicle matures, it ○ Highest level of progesterone (primarily) with produces high levels of estrogen, estrogen which eventually triggers a surge in ○ These hormones keep the integrity and Luteinizing Hormone (LH). thickness of the endometrial lining 2. Ovulation (Around Day 14) Thickest at this point ○ Overview: Ovulation is the release of the ○ Prepared for future implantation and support mature egg (oocyte) from the dominant of the development of the embryo follicle in the ovary, triggered by a surge in In the event that the ovulated oocyte is not fertilized, it LH. will undergo degeneration ○ Hormones Involved: ○ Decline of progesterone and estrogen Luteinizing Hormone (LH): The ○ Endometrial lining will no longer be increase in estrogen from the maintained dominant follicle causes a rapid ○ Followed by the bursting of blood vessels surge in LH. This LH surge prompts ○ Result in the menstrual flow (towards the the mature follicle to release its end of the menstrual cycle) egg. Interplay of ○ Process: ○ gonadotropic hormones The dominant follicle ruptures, FSH releasing the egg into the fallopian LH tube. ○ sex hormones The egg then begins its journey Progesterone toward the uterus, where it may Estrogen meet sperm and be fertilized. The secretory phase is the most stable 3. Luteal Phase (Days 15-28) The length of menstrual flow can vary ○ Overview: After ovulation, the ruptured ○ Menstrual and proliferative phase phase follicle transforms into the corpus luteum, ○ A range (check graph) which secretes hormones to support the Ideally uterine lining and maintain pregnancy if ○ 28-day cycle (28-14) fertilization occurs. ○ Ovulation can happen on the 14th ○ Hormones Involved: ○ It can be later or later Progesterone: The corpus luteum Can be 3 days earlier produces progesterone, which Safe days to not get pregnant stabilizes and maintains the ○ Proliferative days (before the 11th) thickened endometrial lining, ○ After the 17th day onward creating an ideal environment for a fertilized egg. OVARIAN CYCLE Estrogen: The corpus luteum also The ovarian cycle is a series of changes that occur in the produces some estrogen to further ovaries to prepare for potential fertilization and pregnancy. It support the endometrial lining. ○ Process: YSABELA ANGELA FERNANDEZ 17 If fertilization occurs, the corpus luteum continues to produce progesterone to maintain the pregnancy until the placenta takes over. If fertilization does not occur, the corpus luteum degenerates, leading to a drop in progesterone and estrogen levels. This hormonal decrease causes the endometrial lining to shed, marking the beginning of menstruation and the start of a new cycle. Summary of Phases: Follicular Phase: Follicles mature, estrogen levels rise, and the uterine lining thickens. Ovulation: Release of the mature egg from the ovary Luteal Phase: Corpus luteum forms, secretes hormones to support a potential pregnancy, and if pregnancy does not occur, hormone levels drop, leading to menstruation. LH’s role in stimulating the release of oocyte from the granulosa cells ○ The hormone for ovulation YSABELA ANGELA FERNANDEZ 18 VARIATIONS IN THE LENGTH OF MC/PHASES Most cycles: 25 to 30 days ○ >25d Older women ○ 15-18 years old = 30d ○ 30 years old = 30 days ○ 35 years old = 28 days 25, 28, 30 day cycles SUMMARY OF HORMONE EFFECTS FSH ○ Stimulates the growth & development of the follicle ○ Stimulates secretion of estrogen ○ Enhances effect of LH in stimulation ovulation LH ○ Stimulates the final development of the follicle ○ Stimulates the ovulation ○ Stimulates the development of the corpus luteum ○ stimulates the production of progesterone Estrogen ○ Stimulates repair of uterine lining ○ Inhibits release of FSH ○ Inhibits release of LH ○ Falls in concentration results in menstruation ○ Fall in concentration removes inhibition of FSH and a new cycle begins YSABELA ANGELA FERNANDEZ 19

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