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Preclineazy Sahana Mahesh EMBRYOLOGY ANATOMY REVIEW FERTILIZATION GASTRULATION, NEURULATION SOMITOGENESIS TERATOLOGY ~ 30 MINUTESTHE FEMALE REPRODUCTIVE TRACT bioninja.com THE FEMALE REPRODUCTIVE TRACT UTERUS OVIDUCT OVARY FIMBRIAE ENDOMETRIUM CERVIX VAGINA bioninja.com THE FEMALE REPRODUCTIVE TRACT UTERUS OVIDUCT OVARY FIMBRIAE ENDOMETRIUM CERVIX VAGINA bioninja.com QUICK FACTS OVIDUCT Interstitial regionIsthmus (~15%) (~2%) Ampulla (~70%) Much more rarely… Ovarian pregnancy (~3%) MOST COMMON SITE OF Abdominal pregnancy FERTILIZATION IS Cervical pregnancy THE AMPULLA bioninja.com QUICK FACTS UTERUS ENDOMETRIUM NORMAL IMPLANTATION OCCURS IN THE UPPER, POSTERIOR WALLOF THE UTERINE CAVITY bioninja.com THE SPERM ACROSOME • DIGESTIVE ENZYMES EJACULATION • ACROSOMAL REACTION Head NUCLEUS • 23 CHROMOSOMES • 10% sperm, 90% alkaline fluid • FERTILIZATION containing fructose and prostaglandins Middle piece COLLAR • ~3.5 ml semen, ~200-600 million sperm • MITOCHONDRIA per ejaculation • LOCOMOTION • Most sperm deposited at the external os FLAGELLUM of the uterus Tail • LOCOMOTION • Max. life span in female genitourinary PLASMA MEMBRANE • CAPACITATION tract: 24-48 hours REACTION • Motility affected pHTHE OVUM CORONA RADIATA • Granulosa cells • Contribute to corpus luteum formation ZONA PELLUCIDA • Acrosome reaction VIABLE FOR ~24 HOURS POST NUCLEUS OVULATION • 23 chromosomes • Fertilization CORTICAL GRANULES • Hydrolytic enzymes • Cortical reactionEMBRYOGENESIS 1. Sperm deposited at the externalos of the cervix 2. 0.00001% of sperm reach the site of fertilization in the oviduct Movement of sperm facilitated by • Flagellum • Contraction of uterine tube (encouraged by prostaglandins • Cilia of mucosal cells in uterine tube 3. Capacitation reaction MALE FERTILITY CAN BE EVALUATED THROUGH 4. Acrosome reaction MEASURING SPERM MOTILITY. If, for example, 2 hours post-ejaculation, it is found that < 40% of sperm in a semen sample are non-motile, this would raise concerns over the fertility of the individual SPERM CAPACITATION Washing off the glycoproteins proteins from the plasma membrane of the sperm - enable it to penetrate the corona radiata of the ovum and fertilize the ovum Head of sperm interacts with mucosal lining of fallopian tube, enzymes digest away the proteins Hyperactivation of sperm in the oviduct: change in flagellar motion from wavelike to whiplike. Necessary in order for sperm to detach from oviduct epithelium & helps to propel sperm towards eggACROSOME REACTION CORTICAL REACTION CORTICAL REACTION • Fusion of sperm & ovum membranes trigger several cortical granules to be released from the ovum cytoplasm via exocytosis INSERT IMAGE HERE • The granules contain substances that harden the zona pellucida and prevent polyspermy, leading to aneuploidy or polyploidy • Fusion of sperm & ovum membranes 1: 1 polar body also triggers completion of meiosis ii 4: 4 polar body in the oocyte, releasing a polar body, being formed making it’s chromosome number 23 i.e. ready to fertilize FERTILIZATION WHAT IT ACHIEVES: 1. Establishment of diploid number 2. Determination of chromosomal sex of the individual 3. Metabolic activation of ovum and initiation of cleavage (A) Mature human oocyte arrested at metaphase II. The polar body is located beneath the zona pellucida on left of the oocyte. (B) A newly fertilized human oocyte, with male and female pronuclei in the centre and two polar bodies at the left of the oocyte. • RAPID MITOTIC DIVISIONS WITH A LACK OF CLEA VAGE GROWTH • THE EMBRYO ACHIEVES THIS BY SKIPPING THE G1 Zona pellucida AND G2 PHASES OF INTERPHASE MORULA COMPACTION 2 CELL 4 CELL 8 CELL 16 CELL ( DAY 1) ( DAY 2) ( DAY 2.5) ( DAY 3) THE COMPACTED MORULA Outer blastomeres adhere tightly through gap junctions and desmosomes & merge together to become nearly indistinguishable CLEA VAGE MORULA 2 CELL 8 CELL 16 CELL 4 CELL ( DAY 1) ( DAY 2) ( DAY 2.5) ( DAY 3) BLASTOCYST BLASTOCYST BLASTOCYST FORMATION • Fluid accumulates in spaces among the inner blastocoele blastomeres • Fluid-filled space called blastocoele 58 CELL 107 CELL ( DAY 4) ( DAY 5)STAGE OF DEVELOPMENT? STAGE OF DEVELOPMENT? MORULA STAGE OF DEVELOPMENT? MORULA BLASTOCYSTBLASTOCYST “HATCHING” INNER CELL MASS TROPHOBLAST BLASTOCOELE BLASTOCYST ZONA PELLUCIDAEndocrine and Reproductive Physiology, Fifth EditionIMPLANTATION Maternal blood invasion, Will differentiate to eventually become chorionic intervillous space Syncytiotrophsyncytium Human Embryology and Developmental Biology, Sixth Edition DECIDUAL REACTION • The decidua is of maternal origin and refers to the endometrium of the gravid uterus • Connective tissue cells differentiate into WEEK 1 large polygonal cells, which accumulate large stores of glycogen and lipids • involved in the formation of an immunologically favourable environment for the embryo WEEK 10DIFFERENTIATION OF THE INNER CELL MASS epiblast hypoblast Bilaminar disk GASTRULATION The appearance of the primitive node (Hensen’s) and subsequently the primitive streak is the first & most significant signal of CRANIAL gastrulation The streak signifies the formation of the body axis cranial caudal CAUDAL GASTRULATION EPIBLAST HYPOBLAST FORMATION OF TRILAMINAR DISK ALL EMBRYONIC TISSUE ORIGINATES FROM THE EPIBLAST NEURULATION PRIMARY INDUCTIVE EVENT NOTOCHORD FORMATION NEURULATION Starts with formation of neural plate and ending with closure of the neural tube (future brain and spinal cord) NEURAL PLATE FORMATION • Cells differentiate to become taller & more neural in nature • Notice formation of the neural groove that runs down the middle NEURULATION Starts with formation of neural plate and ending with closure of the neural tube (future brain and spinal cord) NEURAL PLATE FORMATION • The neural folds reach together along the centre and join to form a zip-like structure • The zip then closes, but leaves 2 openings at either ends of the embryo: the anterior & posterior neuropores, which eventually closeNEURULATION NEURAL INDUCTION PROTEINS Wnt family Sonic Hedgehog TGF beta family Induce formation of Expressed in notochord and & Bone ectoderm/mesoderm induces neural patterning Morphogenetic derivatives proteins and somite formation Regulate cell differentiation NEURAL CREST DERIVATIVES PNS, SCHWANN CELLS MELANOCYTES ADRENAL MEDULLA CRANNIAL BONES MESODERM NOTOCHORD Things that are sensory and keep you in touchwith the ECTODERM DIFFERENTIATION outside world OUTER ECTODERM NEURAL CREST NEURAL TUBE Epidermis, hair, nails, PNS, adrenal medulla, sebaceous glands, Brain, spinal cord, Olfactory epithelium, melanocytes, motor neurons, retina facial cartilage, mouth epithelium, lens, dentine of teeth cornea SPINA BIFIDA Failure of closure of the neural groove The extent of disability depends on the site and size of the defect Can include abnormalities in lower limb neurology including paralysis, with bladder and bowel dysfunction. SPINA BIFIDA All women wishing to conceive are advised to take 0.4 mg of folic acid daily starting at least a month prior to conception Women at increased risk are advised a 5 mg dose e.g. Type 2 diabetes, raised BMI, on antiepileptic medicationsThe pons and cerebellum originate from which of the following structures? A) Telencephalon B) Diencephalon C) Mesencephalon D) Metencephalon E) MyelencephalonThe pons and cerebellum originate from which of the following structures? A) Telencephalon B) Diencephalon C) Mesencephalon D) Metencephalon E) Myelencephalon REGIONALIZATION OF THE CNS Telencephalon Cerebrum Forebrain Diencephalon Thalamus, hypothalamus Midbrain Mesencephalon Midbrain Hindbrain Metencephalon Pons, cerebellum Myelencephalon Medulla oblongota Spinal cord SOMITOGENESIS • Formation of concentric mesodermal cells • Somites have unique positional Increased number of somites = more values along the body axis, specified progressed development by Hox genes • They are transient structures, but are critical for segmental organization of the axial skeletonSOMITOGENESIS SOMITES SCLEROTOME MYOTOME DERMATOME Cartilage (then bone) of the Cartilage (then bone) of the Cells that contribute to Axial skeleton e.g. Axial skeleton e.g. the connective Vertebrae, ribs Vertebrae, ribs tissue of the dermis • Teratogens act during a critical period Factors determining teratogenesis 1. Dosage: how much of the teratogen the fetus was exposed to TERATOLOGY 2. Time and length of exposure: consider if the exposure occurred during critical periods 3. Genotype of embryo: how well the fetus is innately able to deal with the teratogen when exposed Chromosomal abnormalities: structural or numerical e.g. Cri du Chat, Turner Syndrome Gene mutations: inheritance patterns e.g. achondroplasia, phenylketonuria Environmental factors: exposure to TERATOLOGY teratogens e.g. Rubella, Syphillis, Accutane, thalidomide, tobacco products Radiation RUBELLA INFECTION • Risk greatest between 0-12 weeks post conception • 20% cases spontaneous abortion • 100% risk of congenital abnormalities • Cardiac defects, deafness, retinopathy, cataracts, mental retardation In general, risk of teratogens (including drugs) are greatest in the 1 trimesterWhich of the following are derived from the embryonic mesoderm? A) Pituitary gland B) Melanocytes C) Respiratory epithelium D) Adrenal cortex E) Adrenal medullaWhich of the following are derived from the embryonic mesoderm? A) Pituitary gland B) Melanocytes C) Respiratory epithelium D) Adrenal cortex E) Adrenal medulla