1 Human Embryology – Chapter 1
Embryology: study of the devl’t of an individual before birth Gonads & Gametes
x Gametes: cells that carry out reproduction
x Fertilization: fusion of male spermatozoon and female ovum = zygote Æ embryo Æ fetus Chromosomes
x
o Diploid number = 46 chromosomes Haploid & Diploid Chromosomes
o Gametes = haploid = 23 chromosomes o Zygote = diploid (23 from each parent) x
o 44 autosomes, 2 sex chromos (X or Y) Autosomes & Sex Chromosomes
o Male = XY, female = XX
o Homologous chromosomes: pair of 2 chromos that are exactly alike One chromo of each pair from mother and father
o Chromosome Structure
2 chromatids, 1 centromere (kinetochore)
Karyotyping: classification of chromos based on characteristics (ie: length) o Significance of Chromosomes
Cells get directions from fertilized ovum to carry on all its func’ns throughout life Genes made of DNA store all information; involved in protein synth
Proteins = enzymes, hormones, antibodies; main constituents of body x Func’ns of cell depend on the proteins it synthesizes
x
o Prophase Mitosis
Chromatin condenses Æ Chromos are now seen distinctly; centrioles move apart Nuclear mbrn disappears, spindle forms
o Metaphase
Chromos arranged at equator and att to spindle o Anaphase
Centromeres split so that ea chromatid becomes an independent chromo One chromo of each pair moves to either
o Telophase
Nuclear membranes form Centrioles divide
Chromosomes gradually lengthen and become indistinct o Interphase (in between cell divisions)
Chromos are in the form of extended threads DNA of each chromo has undergone duplication x
o Prophase I: 4 Phases Meiosis I
Leptotene: chromos visible; each has 2 chromatids – can’t distinguish Zygotene: 2 chromos of each pair lie parallel to eo Æ “bivalent” (synapsis) Pachytene: 2 chromatids of ea chromo become distinct
x Bivalent has 4 chromatids = “tetrad”; 2 central & 2 peripheral x Crossing Over bt 2 central chromatids of each chromo
2 x Chiasmata: point of adherence of crossing over
Diplotene: 2 chromos of bivalent try to move apart
x Chromatids involved in crossing over break at points of crossing and loose pcs attached to other chromatid = genetic exchange
o Metaphase I
nuclear mbrn disappears
spindle forms and chromos are att to it by centromeres o Anaphase I
One entire chromosome of the pair moves to either pole Centromeres do not divide
o Telophase I
2 haploid daughter cells formed
x Interphase bt Meiosis I and II has NO DNA DUPLICATION x
o Similar to mitosis but all 4 daughter cells are genetically different due to crossing over Meiosis II
Spermatogenesis and Oogenesis Human Embryology – Chapter 2
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Structure of a Mature Spermatozoon x Head
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o Derived from nucleus (23 highly condensed chomos)
Chromos extremely condensed Æ head highly resistant to physical stresses Chem. Basis for condensation is replacement of histones by protamines
o Acrosome: cap-like structure Æ has enzymes that help penetration of spermatozoon into ovum during fertilization
x Neck
o Basal body: helps est intimate connection bt head & remainder of spermatozoon Made of 9 segmented rod-like structures
Articular surface on proximal side (towards head) which fits into a depression (implantation fossa) in head
o Centriole x Axial Filament
o Begins just behind centrioel; passes thru middle pc and most of tail o Annulus: ring-link structure through which axial filament passes through
o Spiral sheath: made up of mitochondria, surrounds the part of axial filament in mid pc o Composed of many fibrils, arranged in a circle
Pair of central fibrils surrounded by 9 doublets Petal-shaped fibrils – 1 outside each doublet
Fibrous sheath outside fibrils (surround by spirally arranged mito in middle pc) x Entire spermatozoon enclosed in plasma mbrn
x Formation of spermatozoa during reprod period in males (from 12-16 thru old age) Spermatogenesis
x Formed in walls of seminiferous tubules of testes x Spermatogonia (type A) or germ cells - DIPLOID
3 o Divide mitotically = Type A & Type B spermatogonia
x Spermatogonia (type B) – DIPLOID
o Enlarge or undergo mitosis to form primary spermatocytes x Primary spermatocytes – DIPLOID
o Divide so that each forms 2 secondary spermatocytes (haploid) o First meiotic division
x Secondary spermatocyte – HAPLOID o Divides to form 2 spermatids
o 2nd meiotic division – NO REDUCTION IN CHROMO # x Spermatid – HAPLOID
o Transformation Æ Each gradually changes its shape to become a spermatozoon
o Spermatid = circular cell containing a nucleus, Golgi apparatus, centriole & mitochondria x SPERMIOGENESIS
o Process of transforming spermatid Æ spermatozoon o Nucleus Æ head
o Golgi Apparatus Æ acrosomic cap
o Centriole Æ divides into 2 Æ one becomes spherical on neck other basal body or annulus Axial filament grows out of them
o Part of axial filament bt neck & annulus becomes surrounded by mito Æ middle piece o Remainder of axial fil. Extends to form tail
o Most of the cytoplasm is shed, but cell mbrn still covers spermatozoon x Spermatogenesis + Spermiogenesis = 2 months
x Maturation & Completion of Spermatozoa
o Current of fluid in seminiferous tubules carries spermatozoa from testis Æ epididymus o Stored and undergo maturation in epididymus
o Changes take place in glycoproteins of PM covering sperm head
o Become fully motile after ejaculation when mixed with prostate & seminal vesicle secr’n o Capacitation: Acquire ability to fertilize ovum after they have been in female genital
tract for some time – final step of maturation
Glycoprotein coat and seminal proteins lying over surface of sperm altered Usually undergo capacitation in uterus or uterine tube
When comes in contact with zona pellucida, changes take place in mbrns over acrosome and enable the release of lysosomal enzymes – acrosome reaction Some enzymes help in digesting the z.p and in penetration of sperm thru it Zona reaction: changes in properties of zona pellucida
x Spermatogenesis vs. Spermiogenesis o Spermatogenesis
1st & 2nd meiotic division AND spermiogenesis : complete process of formation of a sperm from spermatogonium o Spermiogenesis: process of transformation of a rounded spermatid to a spermatozoon
x Cortex of ovary: mainly large round cells Æ oogonia – all to be used in female life is produced before birth and do not multiply thereafter
Oogenesis
x Spermatogenesis vs. Oogenesis
o One primary oocyte only forms ONE OVUM
o When spermatocyte divides, its cytoplasm is equally distributed bt the 2 secondary ones o When oocyte divides Æ almost ALL cytoplasm goes to daughter cell = 2ndary oocyte
4 1st polar body formed just to get rid of unwanted chromos
x Further Details
o Late fetal period – primary oogonia enlarge Æ primary oocytes
o At birth – all primary oocytes (~40,000) in prophase of 1st meiotic; remain in Prophase I until they begin to mature and are ready to ovulate
o Female reproductive period bt 12 – 50 yrs
o With each menstrual cycle, few primary oocytes (~5-30) begin to mature and complete first meiotic division shortly before ovulation
o 1st meiotic division = secondary oocyte + 1st polar body o Secondary oocyte Æ Meiosis II
Ovulation while oocyte in metaphase; remains in meta until fertilization Meiosis II completed only if fertilization occurs
If no fertilization degenerates about 24 hrs after ovulation o Only 1 oocyte reaches maturity and is ovulated per cycle
o Dur entire reproductive life of female, only 400 ova discharged x Formation of Ovarian Follicles
o Stromal cells Æ ovarian or Graafian follicles – surround ova and protect them o Some cells of stroma become flattened and surround an oocyte Æ follicular cells o Flattened follicular cells become columnar Æ primordial follicles
o Zona pellucida: homogeneous mbrn appears bt follicular cells & oocyte
o Follicular cells prolif to form several layers = membrana granulosa Æ granulosa cells o A cavity (antrum) appears within the membrane Æ follicle formed
o Cavity rapidly increases in size = wall of granulosa cells becomes thin; oocyte lies eccentrically in follicle surr by cumulus oophoricus
o Discus proligerus: cells that attach oocyte to wall of follicle
o as follicle expands, stromal cells surrounding membrane granulosa become condensed to form theca interna – secrete oestrogen Æ “cells of thecal gland”
o outside theca interna some fibrous tissue becomes condensed to form another covering for follicle – theca externa Æ ovarian follicle fully formed
x Interdependence of Oocyte & Follicular Cells
o Both oocyte and surr follicular cell dependent on eo for further devl’t
o Follicular cells secrete meiotic inhibitory factors, which prevent primary oocytes from maturing beyond prophase of first meiotic division Æ effect can last many years
o Inhibitory factors transmitted to oocyte via gap junctions present bt microvilli of oocytes and of follicular cells (zona pellucida)
o Follicular cells also rsp for growth, metabo, maturation of oocytes o Oocytes resp for proliferation & diff of follicular cells
o Factors produced in oocyte help formation & aturation of Graafian follicles x Ovulation
o Ovum enlarges and follicle ruptures then shed from ovary
o Just before, follicle diam = 15mm, stroma & theca on this side of follicle very thin o Stigma: avascular area appears over most convex point of follicle
o Cells in cumulus oophoricus become loosened by accum of ICF bt them o Factors leading to ovulation
Ĺ/+FRQF = Ĺ activity of collagenase – digests collagen fibers around follicle :
Ĺ prostaglandins = contraction of smooth muscle in ovary wall Ĺ pressure of fluid in follicular cavity
Enzymatic digestion of follicular wall is main factor responsible x Structure of Ovum
5 o Ovum shed from ovary is not fully mature
o Ovum surr by zona pellucida. Some cells of corona radiate seen sticking outside of zona pellucida
No nucleus seen since nuc mbrn dissolved from Meiosis II
Perivitelline space bt z.p & vitelline mbrn (cell mbrn); contains 1st polar body o Ovum very large at time of ovulation
x Fate of the Ovum
o Ovum easily carried into FT by follicular fluid and ciliated cells lining tube
o Slowly travels thru FT Æ uterus (3-4 days), if have sex, sperm Æ tube = fertilization If fertilized Æ embryo Æ implanted in uterine wall
No fertilization Æ ovum dies in 12-24 hrs passes thru uterus into vagina x Corpus Luteum
o Main Function: secrete progesterone & some estrogen o From ruptured follicle, ruptures as follows:
Wall collapses & becomes folded
Follicular cells are small & rounded then rapidly enlarge Æ cells squish together = polyhedral shape Æ cyto filled with lutein (yellow pigment) Æ luteal cells; some cells of theca interna also enlarge & contribute to corpus luteum
Prog secr’ns has to be poured into blood like secr’ns of endocrine glands (ovarian follicle AVASCULAR, but surr theca interna is full of blood vessels)
Blood supplied by theca interna when corpus luteum forms
o Not fertilized Æ corpus luteum persists for 14 days, secretes progesterone; at end of its func’l life, degenerates and forms mass of fibrous tissue Æ corpus albicans
o If fertilized Æ pregnancy; persists for 3-4 mths; corpus luteum of pregnancy may occupy 1/3 – ½ total volume of ovary
Progesterone secreted is essential for maint of pregnancy in first few mths After 4th month, corpus luteum not needed bc placenta begins to secrete prog hCG prevents c.l frm degenerating in early; sec by trophoblast cells of embryo o Ovarian Cycle: series of changes that begin with formation of ovarian follicle and end
with degen of c.l; ~28 days, ovulation on 14th x Fate of Ovarian Follicles
o Follicles that don’t reach maturity undergo degeneration – ovum & gran cells disappear o Interstitial glands (corpora atretica): formed by prolif of theca interna Æ sec estrogen x Ovarian Cycle and Hormones
o Influenced by hormones produced by hypophysis cerebri
o Hormones of theca interna and corpus lutetium influence other parts of reprod sys x Reproductive Period
o
Ovum usually degens 24hrs after ovulation, sperm usually 48 hrs after ejacul’n Viability of Gametes
x Abnormalities of Form
Abnormalities in Formation of Gametes
o Sperm: may be too large or too small, head body or tail duplicated
o Ovum: may have too lg nucleus or 2 nuclei, 2 oocytes may be seen in one follicle x Chromosomal Abnormalities
o Non-disjunction: During Meiosis I, chromos don’t separate in anaphase; chromo has 24 Trisomy: zygote has 47 chromos (3 identical chromos instead of 1 normal pair)
6 o broad face, obliquely placed palpebral fissures, epicanthus,
furrowed lower lip, broad hands, single transverse crease, MR & heart problems
x extra X or Y chromo can give rise to various syndromes assoc with abnormal genital devl’t, MR and abnormal growth
o XXY: abnormal female
o XXY: klinefelter’s syndrome – abnormal male
Male but testes poorly devl’pd = sterility, gynecomastia o XYY: abnormal male
o XXX: 2 masses of sex chromatin – ‘super females’, but poor devl’t o Monosomy: both chromos of pair go to 1 gamete (22 chromos instead of 23)
Zygote Æ45 chromos
x Turner’s Syndrome: only one X chromo o Agenesis of ovaries
o MR, skeletal abnormalities, folds of skin on neck (webbed neck) o One pair may be rep’d by more than 3 chromos
XXXY, XXXXY, XXYY, XXXX
o Triploidy: gamete may be diploid zygote will have 46+23 = 69 chromos o Abnormalities in crossing over
Translocation: part of chromo att to chromo of different pair Deletion: part of chromo may be lost
Duplication: 2 chromos of pair break at unequal distances then joins opposite chromosome; one chromo longer than normal – some genes duplicated, some genes missing
Inversion: pc separating from chromo may get inverted before joining opp chromo, same genes present but sequences disturbed
o Isochromosomes: formed when centromere splites transversely = 2 dissimilar chromos MosaicismMay also occur during segmentation of ovum = fetus with normal &
abnormal chromos
x Gene Abnormalities (Gene Mutations)
o Change in structure of gene may occur at time of gametogenesis = birth defects o Gene Mutation: change in structure & function of gene
The Menstrual Cycle
Human Embryology – Chapter 3
x Perimetrium: outermost layer, made of peritoneum Structure of the Uterus
x Myometrium: makes up main thickness of the wall, made up of smooth muscle x Endometrium: innermost, undergoes changes during menstrual cycle
o Surface covered by lining epith
o Stroma contains uterine glands fills space bt epith & myometrium
o Arteries run vertically towards surface; some spirally and supply whole thickness of endomet, others straight and confined to basal part
x Follicular Phase Phases of the Mestrual Cycle
o Postmenstrual (Days 5-8) o Proliferative (Days 9-18)
7 o Oestrogens produced by developing follicles = changes
o 1st half of menstrual cycle o Ovulation occurs on Day 14 x Luteal Phase
o Secretory/Premenstrual (Days 19-28)
o After ovulation, corpus luteum formed & starts secreted Progesterone o Progesterone + oestrogen = changes in endometrium
o Endomet thick, soft, richly supplied with blood, nutrition provided by u glands o Before next bleeding = ĻSURJ RHVWURJHQVÆ withdrawal of hormones = bleeding x Menstrual (Days 1-4)
o Few hours before, spiral arteries get constricted so blood supply is cut off = ischemia o Degeneration of endometrium & damage to wall of blood vessels
o When arteries relax & blood flows again, leaks out into endomet thru damaged BVs x Sequence of Events
1. Endometrium gradually thickens from 0.5 mm Æ 7 mm
2. Uterine glands lengthen and become convoluted (basal parts stay tubular)
3. During postmenstrual phase, lining cuboidal, during proliferative, columnar. Glycogen accumulates in basal portion = nucleus pushed towards lumen; apical part of cell shed during secretory phase Æ cell becomes cuboidal again with luminar edge irregular 4. as endometrium thickens, stroma can be divided into 3 layers:
a. Stratum compactum Æ superficial part of stroma
b. Stratum spongiosum Æ stroma surrounding uterine glands c. Stratum basal Æ deepest part of stroma
5. arteries of endomet grow dur prolif phase; dur secretory phase, arteries supplying
superficial 2/3 called spiral arteries. Basal 1/3 doesn’t change in cycle – remains straight & short.
x If no pregnancy: stratum compactum & spongiosum shed off = bleeding x Cervical mucosa is not affected
x Time of Ovulation in Relation to Menstruation o Occurs on Day 14 – middle of cycle
o Body temp low during menstruation, subsequently rises
o Sudden fall in temperature followed by a rise = OVULATION
x Importance of determining the Time of Ovulation and ‘Safe Period’ Clinical Correlation
o
x After ovulation, ovum can be fertilized within 2 days Where pregnancy is not desired
x Sperm die within 4 days after entering vagina
x Fertilization only occurs if have sex bt 4 days before & 2 days after ovulation o
x Knowledge important in cases of sterility; couple can be advised when to try Where pregnancy is desired
x Correlation bt Ovarian & Uterine Cycles o Both are 28 days long
o Uterine cycle dependent on ovarian cycle
o Uterine endomet shows cyclic changes – dependent on hormones secreted by developing ovarian follicles & corpus luteum of ovary
8 x Hypothalamus = major control center of reproduction
o GnRH controls secretion of gonadotrophic hormones by anterior pituitary FSH Æ stimulates formation & maturation of ovarian follicles
x Maturing follicles secrete oestrogens = repair & prolif of endomet
x Oestrogens peak 2 days before ovulation = LH surge 24-36 hrs b4 ovul’n LH Æ ovulation & Graafian follicle transformed into corpus luteum
x Stimulates secr’n of progesterone from corpus luteum
x Combined action of oestrogen & progesterone stimulates endometrial glands to secrete glycogen rich mucoid material
x No fertilization Æ granulosa cells produce inhibin Æ ant pit Æ inhibits secretion of GnH = regression of corpus luteum
o Fall in blood level of estrogen & progesterone o Endometrum regresses Æ menstruation
x Fertilization Æ no regression; progesterone & oestrogen cont to be secreted
x Use of Hormones for Contraception Clinical Correlation
o Progestins: synthetic; better results when small amount of oestrogen given o Norethisterone acetate (1 mg) + oestradiol (50 ȝJ
Pack of 28 Æ 21 = hormonal, 7 = nothing Start 5 days after onset of menstruation
o Progesterone inhibits FSH & LH secretion Æ interferes with maturation of follicles & ovulation
o Stopping use = withdrawal of hormones Æ menstruation Formation of Germ Layers
Human Embryology – Chapter 4
x Morula: 16 cells
x Trophoblast: outer layer of cells covering inner cell mass of morula x Blastocyst: fluid partially separates inner cell mass from trophoblast
x Embryonic disc: formed by rearrangement & multiplication of cells of inner mass o 2 germ layers Æ ectoderm & endoderm
o Mesoderm forms later between endo & ecto
x Amniotic cavity: formed on ectodermal & endodermal sides = yolk sac x Extra-embryonic mesoderm: separates walls of cavity from trophoblast x Extra-embryonic coelom: splits e-e meso into 2 layers:
o Somatopleuric Æ in contact with trophoblast o Splanchnopleuric Æ in contact with yolk sac x Chorion: trophoblast + somatopleuric
x Amnion: cells forming wall of amniotic cavity
x Connecting Stalk: attaches amniotic cavity to trophoblast x Prochordal Plate: ectoderm & endoderm not separated x Primitive Streak: embryonic disc divided into right & left
x Mesoderm: formed by cells multiplying in primitive streak Æ bt endo & ecto x Cloacal Membrane: caudal to primitive disc Æ only endo & ecto
9 x Occurs at the ampulla of uterine tube; only 1 sperm penetrates zona pellucida
Fertilization
x As soon as sperm enters ovum, meiosis II is complete x Female pronucleus: nucleus of ovum after fertilization
x Male pronucleus: transformation of head of sperm after separates from middle piece and tail x Pronuclei lose their nuclear membranes and chromos from each get mixed together
x Mitosis = 2-celled embryo
x Biochemical Changes Occuring during Fertilization
o Glycoprotein of zona pellucida = induction of acrosomal reaction Æ penetrate thru z.p o Plasma mbrns of sperm & oocyte fuse at receptor sites; head & tail enter cyto of ovum o Changes in PM of oocyte & z.p ensure that no other sperm can enter oocyte
o Zona reaction: z.p altered due to release of lysosomal enzy by PM of oocyte o As soon as sperm enters ovum – Meiosis II complete & 2nd polar body formed o Entry of sperm = metabolic changes within ovum Æ devlp into embryo
o Before mitosis, each pronuclei undergoes DNA replication to form 2nd chromatid o Mitosis = 2 cells with 46 chromos (from sperm AND ovum)
o As a result of fertilization Diploid number restored Determination of sex
Fertilized ovum undergoes cleavage (divides into many cells) o 2 daughter cells are still surrounded by zona pellucida
o Each daughter cell is much smaller than ovum
o As embryo divides more and more, cells become smaller and smaller x Test Tube Babies
o In vitro fertilization
o Gonadotroins admin’d to woman to stimulate growth of follicles in ovary
o Ovum removed by an aspirator just before ovulation then added with sperm in a medium o Fertilization and early devl’t of embryo take place in medium
o Embryo moved to uterus when reaches 8-cell stage
x Girl Æ sperm is X-bearing, zygote = 44 + X + X Sex Determination
x Boy Æ sperm is Y-bearing, zygote = 44 + X + Y x Determined at fertilization
x One cell divides at a time Cleavage
x Morula: 16-cell stage, still surrounded by z.p o Inner cell mass Æ “embryoblast”
o Outer layer Æ trophoblast – help provide nutrition to embryo
x Fluid from uterine cavity separates layers of morula; as fluid increases Æ cyst x Blastocyst: cells of trophoblast flattened & inner mass att on one side of trophoblast
o Blastocoele: cavity of blastocyst
o Embryonic/animal pole: side that is att to inner cell mass o Abembryonic pole: opposite side
x Function of Zona Pellucida
o Trophoblast can stick to epithelium and its cells can ‘eat up’ other cells Can invade and burrow into tissues which it contacts
10 Z.p prevents it from sticking as it moves down tube; receives substances stored
within ovum (yolk) & by diffusions from uterine secretions
blastocyst needs additional sources of nutrition Æ sticks to uterine endometrium o z.p disappears after morula reaches uterine lumen
o z.p prevents implantation of blastocyst at an abnormal site
o z.p acts as barrier that separates embryonic & maternal tissues to prevent immunological reactions
when z.p disappears, various immunosuppressive cytokinase and proteins are produced by implanting embryo – blocks mother from thinking its foreign
x embryonic disc: 3-layered Æ endoderm, ectoderm, mesoderm Formation of Germ Layers
1. Formation of endoderm Æ some cells of inner cell mass flattened 2. Formation of ectoderm Æ remaining cells of inner cell mass columnar
3. Amniotic cavity: space between ectoderm (below) & trophoblast (above) a. Amniotic fluid fills cavity
b. Amniogenic cells derived from trophoblast, line roof of cavity c. Floor formed by ectoderm
4. Heuser’s membrane: lining of flattened cells from endoderm inside blastocystic cavity a. primary yolk sac Æ cavity lined on all sides by cells originated from endoderm 5. Extra-embryonic mesoderm: originate from cells of tropho; lies bt tropho and flattened endo
cells around yolk sac and also separates wall of amniotic cavity from trophoblast a. Lies outside embryonic disc, doesn’t give rise to any tissues of embryo 6. Extra-embryonic coelom: splits e-e meso into 2 layers
a. Parietal/somatopleuric extra-embryonic mesoderm: lines inside tropho & outside amniotic cavity
b. Visceral/splanchnopleuric extra-embryonic mesoderm: lines outside yolk sac
c. Connecting stalk: unsplit part of meso, keeps devlp’g embryo attached to blastocyst wall 7. Formation of Chorion & Amnion
a. Chorion: mbrn formed by parietal e-e meso & trophoblast
b. Amnion: mbrn constituted by amniogenic cells = wall of amniotic cavity c. Important role in child birth
8. Secondary Yolk Sac: e-e meso & e-e coelom Æ sac becomes much smaller; cuboidal cells 9. embryo = circular, 2 layers (endo twrds yolk sac = cuboidal & ecto near amniotic cav, columnar 10. prochordal plate: area of endoderm where cells become columnar = central axis of embryo;
divided into right & left and can distinguish future sites of head & tail
11. primitive streak: bulge formed when ectodermal near central axis near tail-end begin to proliferate; from rounded or oval swelling, becomes linear structure in central axis of disc 12. cells proliferating near prim streak push themselves bt endo & ecto Æ intra-embryonic meso 13. meso extends cranial to prochordal plate – becomes cont’s across midline; forms most of tissues
of body; no meso in prochordal plate – region very thin Æ bucco-pharyngeal mbrn 14. disc and primitive streak gradually elongate
15. as embryonic disc enlarges – connecting stalk becomes smaller & confined to tail end of disc 16. cloacal membrane Æ mesoderm from primitive streak passes thru into connecting stalk Alternative
x ectoderm (columnar) Æ epiblast View of Formation of Germ Layers x endoderm (cuboidal) Æ hypoblast
11 x some cells of epi- migrate to primitive streak Æ mesoderm
x other cells push hypoblast aside = endoderm and those that remain = ectoderm x all 3 germ layers derived from epiblast
x prochardal plate and neural crest also form some intra-embryonic mesoderm Use of Stem Cells in Treatment of Diseases
x embryonic stem cells: cells of inner cell mass, differentiate into 3 layers Æ all tissues & organs x can be grown in culture Æ various adult cells
x when introduced in tissues of living person, local enviro helps cells diff into surr cell types x Used to treat many diseases:
o Parkinson’s o Alzheimer o Diabetes o Myocardial infarction o Blood diseases o Severe burns o Osteoporosis
o Spinal cord injury…
x Immune rejection is possible Æ under study “therapeutic stem cell cloning”
x Adult stem cells can be taken from bone marrow, brain, skeletal muscle Æ difficult in culture Timetable of Events
x Pre-organogenesis period: devl’t from fertilization Æ formation of bilaminar disc (14 days) o Teratogens introduced dur this period = death
x Gastrulation: primitive streak, intra-embryonic meso (begins in 3rd week)
x Embryonic period: from 3rd week; teratogens introduced here Æ congenital anomalies Age (days) Developmental Events
2 Embryo at 2-cell stage
3 Morula formed
4 Blastocyst formed 8 Bilaminar disc formed
14 Prochordal plate & primitive streak seen
16 Intra-embryonic mesoderm is formed/disk is now 3-layered.
Further Development of Embryonic Disc Human Embryology – Chapter 5
x Primitive knot: enlargement of cranial end of primitive streak
x Notochordal process: cells of primitive knot multiply & pass cranially = rod-like structure that reaching up to prochrodal plate
x Notochord: formed when prochordal plate converted back into rod-like structure x Nucleus pulposus: remnants of notochord; found in each intervertebral disc
x Neural plate: wide strip of ectoderm overlying notochord that becomes thickened, brain & spinal cord develop from here
x Intra-embryonic mesoderm = 3 subdivisions
12 o Lateral plate mesoderm
Intra-embryonic coelom: cavity that splits meso into somatopleuric (contact with ectoderm) & splanchnopleuric layers (contact with endoderm)
x Later forms pericardial, pleural & peritoneal cavities
o Intermediate mesoderm: strip of mesoderm bt lateral plate & paraxial mesoderm x Head & tail folds & lateral folds of embryonic disc Æ foregut, midgut, hindgut
x Buccopharyngeal membrane: prochordal plate that closes cranial end of gut x Cloacal membrane: closes gut caudally
x Umbilical cord: develops from connecting stalk; covered by amnion
o R & L umbilical arteries, L umbilical vein, remnants of vitello-intestinal duct & yolk sac o Ground substance made of Wharton’s jelly from mesoderm
x Allantoic diverticulum: from yolk sac b4 form’n of gut; after tail fold Æ diverticulum of hindgut x Pericardial cavity: from intra-embryonic coelom that lies cranially to prochordal plate;
developing heart is ventral
o After head fold, pericardial cavity lies ventral to foregut & developing heart is dorsal to pericardial cavity
x Septum transversarum: made of intra-emb meso that lies cranial to pericardial cavity; after head fold, caudal to pericardium & heart; liver & diaphragm devl’p in relation to septum transversum
x Notochord: midline sstructure, develops in region lying bt cranial end of primitive streak 7 caudal end of prochordal plate; several stages of development:
Formation of the Notochord
o Cranial end of primitive streak becomes thickened Æ primitive knot o Blastopore: depression that appears in center of primitive knot
o cells in primitive knot multiply and pass cranially in middle line between ectoderm & endoderm Æ caudal margin of prochordal plate Æ notochordal process
o cells of notochordal process undergo several stages of rearrangement Æ notochord x elongates as embryo grows; lies in area where spine will go, BUT notochord does NOT give
rise to vertebral column; most of it disappears, but parts persist in region of each intervertebral disc Æ nucleus pulposus
x More Details…
o After blastopore is formed, cavity extends into notochordal process Æ notochordal canal o Cells forming floor of canal become intercalated with endo cells Æ separate canal from
cavity of yolk sac
o Floor of canal begins to break down to comm. w/ yolk sac, and amniotic cavity (through blastopore) Æ amniotic cavity and yolk sac are now in communication with e.o
o Walls of canal gradually flatten Æ notochordal plate
o Flattening process reversed and plate becomes curved again = shape of tube; prolif of cells of tube Æ solid rod of cells Æ notochord; complete separated from endoderm
x Neural tube gives rise to the brain & spinal cord Formation of the Neural Tube - Neurulation
x From ectoderm overlying notochord & extends from prochordal plate Æ primitive knot x Divides into:
o Cranial enlarged part that forms brain o Caudal tubular part that forms spinal cord
13 x Separates ectoderm and endoderm except in:
Subdivision of Intra-Embryonic Mesoderm o Prochordal plate
o Cloacal membrane
o In midline caudal to prochordal plate (place for notochord)
x Mesoderm meets cranially to prochordal plate at midline, continuous with e-e meso, divides into: o Paraxial mesoderm: on either side of notochord, becomes thick
Becomes segmented into cubical masses Æ somitomeres Æ somites First somites seen on either side of midline behind prochordal plate More somites formed caudally on either side of developing neural tube o Lateral plate mesoderm: more laterally, forms thinner layer
o Intermediate mesoderm: between paraxial & lateral
x Intra-embryonic coelom: cavities that appear in lateral plate meso come together Formation of the Intra-Embryonic Coelom
x 2 haves joined together crania to prochordal plate
x Comm. with extra-embryonic coelom Æ lat. Plate meso slpits:
o Somatopleuric/parietal: i-e mes that is in contact with ectoderm
o Splanchnopleuric/visceral: i-e embryonic meso that is in contact with endoderm o Septum transversum: 2 divisions continuous cranial to cardiogenic area bc i-e coelom
hasn’t extended into it
x i-e coelom Æ pericardial, pleural & peritoneal cavities
o pericardium: formed from part of i-e coelom in midline, cranial to prochordal plate o cardiogenic area: cranial to cardiogenic area
x primary yolk sac Æ bounded above by cubical endoderm of embryonic disc and flattened cells of blastocystic cavity everywhere else
Yolk Sac and Folding of Embryo
x secondary yolk sac Æ smaller with formation of e-e meso and e-e coelom x progressive increase in size of embryonic disc
x head & tail of disc remain close together = ĹOHQJWKRIGLVFÆ bulge upwards into amniotic cavity x disc grows bigger Æ folded on itself at head & tail Æ head & tail folds
x folds = enclose parts of yolk sac w/in embryo Æ primitive gut – tube formed by endoderm x only midgut communicates with yolk sac; foregut (cranial) & hindgut (caudal) don’t comm. x comm. to yolk sac becomes narrower and narrower Æ definitive yolk sac
x vitello-intestinal duct Æ narrow channel that connects def yolk sac to gut; eventually disappears x lateral folds Æ encloses embryo all the way around by ectoderm
x umbilical opening: except in the region where intestinal duct passes
x as embryonic disc folds on itself, gets bigger Æ surrounds embryo on all sides; embryo floats in amniotic fluid in cavity
x embryo & amniotic cavity & yolk sac remain in tact to trophoblast by e-e meso Æ conn. Stalk Connecting Stalk
x only connecting link bt embryo and placenta
x as embryo grows, area of attachment of stalk becomes smaller; only seen at caudal end o att moves with tail end to ventral aspect of embryo & attached in area of umb opening x blood vessels in embryo comm. with BVs in placenta thru connecting stalk
14 o amnion has circular att to margins of umbilical opening Æ wide tube for:
Vitello-intestinal duct & remnants of yolk sac
E-e meso of stalk; converted into Wharton’s jelly – protects BV in umbilical cord BVs from embryo Æ placenta
Small part of extra-embryonic coelom
x Umbilical cord: progressively lengthens so embryo can move w/in amniotic cavity o at birth: umbilical cord ~0.5 m long, ~2cm diam
o umbilical cord that is too short or too long = problems during delivery
x arises from yolk sac before tail fold; caudal end of embryonic disc Allantoic Diverticulum
x after tail fold, part of diverticulum absorbed into hindgut into connecting stalk x leads to devl’t of urinary bladder
x before formation of head & tail folds, structures at midline from cranial Æ caudal: Effect of Head & Tail Folds on Positions of Other Structures
o septum transversarum
o developing pericardial cavity and heart o prochordal plate
o neural plate o primitive streak o cloacal membrane
x after head fold, pericardial cavity comes to ventral side of embryo Æ heart in roof of cavity; pericardium grows and forms bulging on ventral side of embryo
x septum transversarum caudal to heart; later Æ diaphragm & liver devl’p in relation to septum x prochordal plate Æ buccopharyngeal (oral) closes foregut; when breaks down, comm. w/ ext x most cranial structure becomes enlarged cranial part of neural tube Æ brain
o 2 big bulgings on ventral aspect of embryo: Cranial: developing brain
Slightly below: pericardium
Stomatodaeum: depression bt brain & heart; floor = buccopharyngeal mbrn x Primitive streak now inconspicuous twrds tail end of embryo, gradually disappears
o Distal end of hindgut closed by cloacal mbrn (first caudally, then faces ventrally)
x In later life, remnants of primitive streak Æ tumors that have tissues from all 3 germ layers; mostly seen in sacral region – sacrococcygeal tumors
Additional Points
x Formation of neural tube induced by notochord
x Somitomeres are not confined to region of somits; in head, somitomeres Æ mesenchyme x Wharton’s jelly rich in proteoglycans
Timetable of Events in this Chapter
Age (days) Developmental Events 15 Primitive streak appears Definitive yolk sac formed
15 Allantoic diverticulum is seen
19 Intra-embryonic mesoderm is being formed Connecting stalk can be distinguished 21 Neural groove is seen Head fold begins to fold
23 Closure of neural tube is seen
The Placenta
Human Embryology – Chapter 6
x Implantation: developing embryo gets attached to endometrium
x Interstitial implantation: embryo is buried into the wall of the endometrium x Decidua: refers to endometrium after implantation
x Placenta: formed from embryonic structures & decidua Æ transport nutrients & oxy to fetus; removal of waste products also occurs through placenta
o Chorionic villi: surr by maternal blood, fetal blood circulates thru capillaries in villi o Placental membrane: separates maternal & fetal blood
o Chorion: fetal tissue that contributes to formation of placenta; trophoblast on e-e meso x Trophoblast proliferates into 2 layers:
o Cytotrophoblast - cellular
o Syncytiotrophoblast – cytoplasm with nuclei, but no cell boundaries x Primary villi: central core cytotrophoblast covered by syncytiotrophoblast x Secondary villi: 3 layers, e-e meso Æ cytotrophoblast Æ syncytiotrophoblast x Tertiary villi: blood capillaries in e-e mesoderm
x Maternal blood flows through intervillus space; as placenta enlarges, septa grow & divide placenta into lobes; fully formed placenta = 6” diameter & 500g wt
x Placenta praevia: when placenta attaches lower in body of uterus (vs. upper) Æ problems x Amniotic cavity Æ as grows bigger, e-e coelom goes away & amnion & chorion fuse; as
enlarges further, uterine cavity obliterated & amnion & chorion (membranes) bulge into cervix x Extra-embryonic coelom
x Uterine cavity Implantation
x Zygote is already at morula stage by the time it reaches the uterus Æ 6
th day of fertilization
x z.p prevents the zygote from sticking to the wall of the tube
x when z.p disappears, the trophoblastic cells allow the zygote to attach itself on the uterine wall x interstitial implantation: trophoblast of blastocyst embeds itself deeper and deeper into endomet x proteolytic enzymes are produced by trophoblast to aid in implantation
x trophoblastic cells that are over the inner cell mass, penetrate the epith of endometrium
x mutual interaction bt trophoblastic cells & endometrium mediated by receptors present on uterine epith & secretion of L-selectin, & integrins by trophoblast cells
x when morula reaches uterus, endometrium in secretory phase, these features stay once implantation occurs to support zygote
Decidua
x decidual reaction: stromal cells enlarge, become vacuolated to store glycogen & lipids x decidua basalis: aka decidual plate; portion of decidua where placenta will form
16 o firmly united to chorion
x decidua capsularis: separates embryo from uterine lumen x decidua parietalis: lines rest of uterine cavity
x upon delivery, decidua shed off with placenta and membranes
x surrounded by maternal blood Formation of Chorionic Villi
x capillaries inside villi circulate fetal blood
x exchanges bt maternal & fetal circulations take place thru tissues in walls of villi x projections of trophoblast and extra-embryonic meso; grow into surrounding decidua x villi that go into decidua capsularis degen & this part of chorion smooth Æ chrion laevae x villi that grow into basalis form disc-shaped mass Æ chorion frondosum Æ placenta x Primary Villi: central core of cytotropho surr by syncytiotrophoblast
x Secondary Villi: 3 layers Æ syncytiotrophoblast Æ cytotrophoblast Æ e-e meso x Tertiary Villi: blood capillaries in mesoderm
x Syncytiotrophoblast grows rapidly and becomes thick; lacunae appear and gradually lie radially around blastocyst; they are separated by trabeculae (partitions of syncytium)
o Lacunae gradually comm. w/ eo Æ form’n of large lacunar space surrounding trabeculus x Syncytiotrophoblast grows into endometrium which has eroded so that some of its BVs are
open-up Æ blood fills lacunar space
x Cytotrophoblast cells begin to multiply and grow into each trabeculus Æ central core Æ primary x E-e meso invades center of each primary villus Æ secondary villi
x Blood vessels formed in meso in core of each villus Æ tertiary
x Fetal blood circulates through villi and maternal blood through intervillous space
x Cytotrophoblastic shell: layer of cells that emerge through syncytium of each villus; spread out to form layer that completely cuts off syncytium from decidua; these cells rapidly multiply and placenta grows larger
x Anchoring villi: villi first formed attached to embryonic meso on fetal side and to maternal side on cytotrophoblastic shell
o Truncus chorii: stem of anchoring villi
o Ramuli chorii: fine branches of truncus; attached to cytotrophoblastic shell
o Free villi branch off into intervillous space – whole space filled with villi = increased surface area for exchanges bt maternal & fetal circulation
x Maternal cotyledon: refers to each lobe of placenta, separated by septa; approx 15-20 lobes Further Development of Placenta
x Each lobe has anchoring villi and corresponding branches, Fetal cotyledon (~60-100 in placenta) x At 9 months, placenta ~6-8” diameter & 500g
x After delivery, shed off with decidua; maternal surface (formed by decidual plate) is rough and subdivided into cotyledons
x Fetal surface (chorionic plate) lined by amnion; smooth, umbilical cord att to this surface x Placental Membrane
o Separates maternal from fetal blood; made up of layers of villus wall: x Endothelium of fetal BVs & its basement mbrn
x Surrounding mesoderm (connective tissue) x Cytotrophoblast & its BM
17 x Syncytiotrophoblast
o All interchanges of oxygen, nutrition & waste take place here
o Total area ~ 4-14 sq m Æ greater surface area = more effective exchanges
o Efficiency increased in later part of pregnancy when cytotropho layer disappears and CT thins so that thickness of mbrn goes from 0.025 mm thick Æ 0.002 mm
o Towards end of pregnancy, fibrinoid deposit appears which reduces efficiency x Functions of Placenta
o Transport of O2, water, electrolytes, carbs, lipids, polypeptides, AAs & vitamins from maternal Æ fetal blood; full term fetus takes upto 25 mL O2/min
o Excretion of CO2, urea & other waste products from fetus Æ maternal blood o Maternal Abs (IgG) = immunity against some infections (ie: diphtheria & measles) o Prevents bacteria and other harmful substances from reaching fetus; but viruses and
bacteria & drugs can pass through Æ congenital malformations
o Maternal hormones don’t reach fetus, but synthesis of progestins & synthetic oestrogens (ie:: diethylstilbestrol) easily cross placenta and can have adverse effects on fetus (even carcinoma in later life)
o Keeps blood streams separate Æ prevents antigenic reactions between them o Synthesizes hormones in syncytiotrophoblast
x Progesterone Æ maint of pregnancy after 4th month (when corpus luteum degens) x Oestrogens (estriol) Æ maternal blood; promote uterine growth and development
of mammary gland
o Human chorionic gonadotropin (hCG) produced by placenta; similar to LH; Gonadotropins excreted through maternal urine Æ used to detect pregnancy
o Somatomammotropin (hCS) has an anti-insulin effect on mother = increased plasma levels of glucose and AAs in maternal circulation; increases availability of these materials for fetus; enhances glucose utilization by the fetus
o Circulation of Blood through Placenta
x Blood flow thru lacunar spaces in syncytiotropho begins at 9th day x Blood enters intervillous space through maternal arteries that open into it;
pressure of blood drives it right to the chorionic plate
x Blood in spaces is drained by veins that also open into these spaces
x In fully formed placenta, intervillous spaces contain ~150 mL of blood which can be replaced in 15-20 seconds (3-4x/min)
x Upper uterine segment Æ fundus & greater part of body; enlarges dur pregnancy; placenta here Normal Site of Implantation of the Ovum
x Lower uterine segment Æ lower part of body
x Abnormal Implantation within Uterus Abnormal Sites of Implantation of Ovum
o Placenta praevia
Problems during delivery Æ severe bleeding; various degrees: : placenta attaches in lower uterine segment
First Degree: attaches in lower segment but doesn’t reach the internal os
Second Degree: margin of the placenta reaches the internal os, ut doesn’t cover it Third Degree: edge of placenta covers the internal os, but when the os dilates
during childbirth, placenta no longer occludes it
Fourth Degree: completely covers internal os & occludes it after dilates x Implantation outside Uterus
18 o Ectopic Pregnancy
Tubal pregnancy: blastocyst is implanted in uterine tube – doesn’t make it to full term & may result in rupture of tube Æ leads to abdominal pregnancy
: ovum gets implanted anywhere outside uterus
Interstitial tubal implantation: blastocyst implanted in part of uterine tube passing thru uterine wall
Implantation in the ovary: fertilization and implantation occur while in ovary x Other Anomalies of Placenta –
o instead of being shaped like a disc, may be: Bidiscoidal: has 2 discs
Lobed: divided into lobes
Diffuse: chorionic villi persist all around blastocyst – placenta thin and not disc Placenta succenturiata: small part of placenta separated from rest of it
Fenestrated: hole in disc
Circumvallate: peripheral edge of placenta covered by circular fold of decidua o Umbilical cord may not be attached to placenta near the center, instead:
Marginal (aka Battledore placenta): cord att to margin of placenta Furcate: blood vessels divide before reaching placenta
Velamentous insertion: BVs att to amnion & ramify before reaching placenta
x Outer wall of e-e coelom formed by chorion & inner wall by amnion
Mutual Relationship of Amniotic Cavity, Extra-Embryonic Coelom & Uterine Cavity
x As amniotic cavity grows, e-e coelom decreases and eventually disappears when amnion & chorion fuse Æ amniochorionic membrane
x As amniotic cavity expands further, uterine cavity gradually disappears as Decidua capsularis fuses with decidua parietalis
x When amniotic cavity grows even more, uterus begins to expand x As amniotic cavity grows, so does the amount of amniotic fluid x Membranes Æ amniochorionic mbrn, decidua capsularis x Childbirth
o As uterine muscle contracts = increased pressure in amniotic fluid Æ membranes bulge into cervical canal until ruptures and fluid flows out of vagina
o After child is delivered, decidua, membranes & placenta are all expelled
x Support for delicate tissues of growing embryo Amniotic Fluid
x Allows for free movement & protection from external injury x Avoids adhesion of fetus to amnion
x Full term = 1 L of amniotic fluid
x Hydramnios: too much amniotic fluid (over 1500 mL)
o Sometimes associated with atresia of esophagus – fetus can’t swallow amniotic fluid x Oligamnios: too little fluid
o Sometimes assoc with renal agenesis Æ no urine added to amniotic fluid
x Both conditions cause complications during delivery and may cause abnormalities in fetus x Constant exchange of water bt amniotic fluid & maternal blood Æ water replaced every 3 hrs x 5th month Æ fetus begins to swallow fluid, absorbed thru gut Æ fetal blood Æ mother
x when fetal kidneys start working , passes urine into amniotic fluid Timetable of Events in this Chapter
19 Age (days) Developmental Events
8 Trophoblast differentiates into cytotrophoblast & syncytiotrophoblast 9 Lacunae appear in syncytium
11 Embryo gets completely implanted in edometrium. 13 Primary villi formed
16 Secondary & tertiary villi are seen 2nd month Villi are seen all around trophoblast 4th month A definitive placenta is formed
Formation of Tissues of the Body Human Embryology – Chapter 7
x Epithelia from ectoderm, endoderm OR mesoderm o Ectoderm Æ epithelia on external
o Endoderm Æ epith lining
surfaces of body & terminal openings to outside gut
o Mesoderm Æ lining of
& organs that develop as diverticula of gut x Mesenchyme = cartilage, bone, muscle, blood, & CTs UGT
o BCs from bone marrow, liver, spleen o Lymphocytes formed in lymphoid tissues
x Endochondral ossification: cartilage later replaced by bone x Intramembranous ossification: direct ossification of membrane x Center of Ossification: where ossification starts
o Diaphysis from primary ossification center
o Epiphyses from secondary ossification center (many at bone ends)
x Epiphyseal plate: separates diaphysis and epiphysis; made up of cartilage, growth in length here x Somites Æ 3 divisions
o Dermatome Æ dermis o Myotome Æ skeletal muscle
o Sclerotome Æ vertebral column & ribs
x Skeletal Muscle derived from somites & mesenchyme of region x Smooth Muscle from mesenchyme related to viscera & blood vessels x Cardiac Muscle from mesoderm related to developing heart
x Neurons & Neuroglial cells from neural tube Epithelial Tissue
x Derived from ectoderm, endoderm or mesoderm : cells arranged like cont’s sheets; line external & internal surfaces of body & cavities o Ectoderm Æ epithelia on external
skin, hair follicles, sweat glands, sebaceous glands, mammary glands surfaces of body & terminal openings to outside epith over cornea & conjunctiva, ext aud meatus, outer tympanic mbrn
epith of some parts of mouth, lower anal canal, terminal parts of male urethra, parts of female external genitalia
o Endoderm Æ lining gut
Entire gut except ectoderm parts of mouth & anal canal & organs that dvl’p as diverticula of gut (ie: liver, pancreas) Auditory tube & middle ear
Respiratory tract
Part of urinary bladder, urethra & vagina o Mesoderm Æ lining of
Tubules of kidneys, ureter, trigone of urinary bladder UGT Uterine tubes, uterus, part of vagina
Testis & its duct system
Endothelium of heart, BVs & lymphatics
Mesothelium lining pericardial, peritoneal & pleural cavities & cavities of joints
x Develop as diverticula from epith surfaces Glands
x Opening of duct usually where original outgrowth from deverticula occurs o Endocrine Æ gland is not associated with epithelial origin
x Proximal part of diverticula become canalized Æ duct system x Distal parts of diverticula Æ secretory elements
x Ectoderm Æ sweat glands, mammary glands x Endoderm Æ pancreas, liver, posterior pituitary x Mesoderm Æ adrenal cortex, anterior pituitary x Mixed Æ prostate, pituitary
x Chondroblasts: form cartilage Mesenchyme
x Osteoblasts: form bone x Myoblasts: form muscle
x Lymphoblasts & haemocytoblasts: form various BCs x Endothelial cells: form BVs & primitive heart tubes
x Remaining mesenchymal cells after formation of tissues Æ various types of CT
x Cells, fibers, ground substance Connective Tissue (CT)
x Formation of Loose CT
o Mesenchymal Æ fibroblasts Æ secrete ground subst, synthesize collagen, reticular & elastic fibers
x Some mesenchymal Æ Histiocytes, mast cells, plasma cells, fat cells
x Occurs before somites appear & continues throughout life Formation of Blood
x 3rd
o Mesodermal cells Æ precursor (haemangioblasts) = BVs & BCs
week Æ formation of BVs & BCs seen in wall of yolk sac around allantoic diverticulum & connecting stalk (clusters of mesodermal cells Æ blood islands)
o Hematopoietic stem cells: formed in center of blood islands = precursor of all BCs o Angioblasts: formed at periphery of islands = precursors of BVs
x Blood cells in yolk sac soon replaced by permanent stem cel;s from mesoderm around developing aorta Æ form colonies in liver
x Late embryonic period Æ formation starts in liver
x Middle of prenatal life Æ definitive haematopoietic SCs from liver Æ colonize bone marrow; x Birth Æ blood formation mainly in bone marrow; totipotent haemal stem cells Æ
pleuripotent haemal & lymphoid stem cells Æ colony forming units (CFU)
x Cells within 1 CFU are committed to diff into one specific line of blood cells Æ RBCs, megakaryocytes, granulocytes, monocytes, macrophages, lymphocytes
o Erythrocytes: burst forming units (BFU) Æ CFU Æ RBCs x Adult Æ bone marrow, lymph nodes, thymus, spleen
x Precursors of blood cells are mesodermal, but blood forming cells differentiating in relatin ot wall of yolk sac & liver may be from endoderm
x Mesenchymal condensation: mesenchymal cells closely packed where cartilage to be formed Formation of Cartilage
x Chondroblasts: rounded mesenchymal cells Æ form cartilage
o Influence intercellular substance of cartilage to be laid down x Chondrocytes: chondroblasts that are trapped within intercellular substance
x Hyaline cartilage Æ collagen fibers present, but can’t see easily x Fibrocartilage Æ many visible collagen fibers
x Elastic cartilage Æ intercell substance permeated by elastic fibers
x Perichondrium: fibrous mbrn around cartilage, formed by mesenchymal cells Bone Formation
x Osteocytes: mature bone cells (bone derived from mesoderm)
x Osteoblasts: bone-forming cells; abundant in regions of bone formation x Osteoclasts: bone-removing cells; seen in regions where bone is absorbed x Intramembranous ossification: directly to bone (ie: skull, clavicle, mandible) Endochondral ossification
1. Mesenchymal condensation at site of bone formation : cartilage Æ bone (ie: long bones)
2. Some mesenchymal cells become chondroblasts Æ hyaline cartilage Æ perichondrium (vascular & contains osteogenic cells)
3. Enlargement of cells where bone formation is supposed to start
4. Calcification of intercellular subst bt enlarged cartilage cells by alkaline phosphatase; primary areolae – empty spaces left behind when nutrition cut off to cell (= death) 5. BVs of periosteum with osteogenic cells (periosteal bud) invade calcified cartilaginous
matrix = wall of primary areolae Æ lg cavities secondary areolae
6. osteogenic cells become osteoblasts Æ around surfaces of plates of calcified cartilage 7. Osteoblasts lay down osteoid (layer of ossein fibrils embedded in gelatinous intercell matrix)
Æ calcified Æ lamellus of bone formed
8. Another layer of osteoid over 1st lamellus then over 2nd… Æ bony trabeculae formed Center of ossifying cartilage is bone; as move away from center, see several layers:
x Region where cartilaginous matrix calcified
x Zone of hypertrophied cartilage cells in uncalcified & surround dead/dying cartilage cells x Normal cartilage with a lot of mitotic activity matrix
1. Mesenchymal condensation in limb bud region Development of a Typical Long Bone
2. mesenchymal condensation Æ cartilaginous model with perichondrium 3. Endochondral ossification starts in shaft Æ primary ossification center 4. Bone formation gradually extends towards ends of shaft – model lengthens 5. osteogenic cells in periosteum lay bone on surface
6. Birth Æ bony diaphysis (shaft) w/ cartilaginous ends; 2ndary oss cntrs appear later in epiphysis of cartilaginous model via intramembranous ossification Æ periosteal collar – gives strength to cartilage model in area of secondary areolae
x As more and more bone is formed on perosteal collar, osteoclasts reabsorb bone (ie: trabeculae) from inside = marrow cavity (doesn’t reach epiphyseal plate)
Growth of a Long Bone
x Most of bone from primary center removed except near ends Æ wall of shaft purely periosteal bone formed by intramembranous ossification
x Layers of Epiphyseal Plate
o Zone of resting cartilage: cells are small, irregular arrangement
o Zone of proliferating cartilage: cells larger & undergo repeated mitosis; columns & ICM o Zone of Calcification: cells larger & matrix becomes calcified
o Zone of dead cartilage cells Æ calcified Æ bone
o When bone has reached full length, cells stop proliferating
o Fusion of epiphysis: bone of diaphysis & epiphysis becomes continuous x Metaphysis: between diaphysis & epiphyseal plate
o Region of active bone formation; highly vascular; no marrow cavity o Calcium-turnover function of bone most active here
o Frequent site of infection
x Interstitial Growth: growth takes place by multiplication of cells (or increase of ICM) o Tissue expands equally in all directions, shape maintained
x Appositional Growth: (ie: bone) growth only by deposition on surface or at ends x Remodeling: removal of unwanted bone in order to give bone its proper shape
x Internal remodelling: arrangement of trabeculae of spongy bone and haversian systems of compact bone change with change in stresses acting on bone
x Dyschondroplasia or endochondromatosis: formation of irregular masses of cartilage w/in metaphysic
Anomalies of Bone Formation caused by
x Exostosis: protrusion of abnormaml masses of bone formed in region of metaphysic
excessive prolif of cartilage cells in epiphyseal plate or failure of normally formed cartilage to be replaced by bone
o Multiple exostosis or diaphyseal aclasis Æ result of interference w/ remodelling of ends x Osteogenesis imperfecta: defective calcification of bone Æ multiple fractures
x Fibrous dysplasia: parts of bone replaced by fibrous tissue
x Osteosclerosis: bones have increased density (ie: osteopetrosis, marble bone disease)
x Achondroplasia: insufficient or disorderly formation of bone in region of epiphyseal cartilage; person becomes dwarf; chondro-osteo-dystrophy Æ limbs fine but vertebral column stays short x Cleido-cranial dysostosis: occurs in membranous bones; clavicle absent and deformities of skull x Dwarfism: generalized underdevelopment
x Gigantism: generalized overdevelopment
x Asymmetric development: all bones of half of body affected
x Paraxial mesoderm segmented Æ somites Æ lie around neural tube Fate of Somites
x Sclerotome: ventromedial; migrate medially
x Dermatome: lateral; migrate & line deep surface of ecto, cover whole body Æ dermis of skin to subcutaneous tissue
Æ vertebral column & ribs
x Myotome: intermediate Æ striated muscle
o Each myotome innervated by 1 spinal nerve in cervical to sacral regions Number of somites formed = number of spinal nerves
o Coccygeal region Æ # somites > # spinal nerves; many degenerate x Occipital somites: (4-5) Æ muscles of tongue, supplied by hypoglossal nerve x Pre-occipital somites: supplied by CN III, IV, VI
x Derived from somites & mesenchyme Striated Muscle
x Myotomes only give origin to musculature of trunk x Occipital myotomes Æ tongue
x Epimere: dorsal part of neck & trunk Æ muscles supplied by dorsal primary ramus o Extensors of vertebral column (muscles of back)
x Hypomere: ventral part of neck & trunk Æ muscles supplied by ventral ramus o Muscles of body wall and limbs
x In-situ from mesenchyme Æ Limb muscles develop in limb buds; ant muscles of abdominal & thoracic walls
x All smooth muscle derived from mesenchyme Smooth Muscle
x Splanchnopleuric mesoderm Æ walls of viscera (ie: stomach)
x Ectoderm Æ muscles of iris (sphincter & dilator pupillae) & myoepithelial cells of sweat glands
x Derived from splanchnoppleuric meso of developing heart tubes & pericardium Cardiac Muscle
x Formed in neural tube
Formation of Neurons & Neuroglial Cells
x Matrix cell layer (aka: primitive ependymal or germinal layer): closest to lumen Æ neurons, neuroglial cells, more germinal cells
x Mantle layer: developing neurons & neuroglial cells
x Marginal zone: no neurons; has reticulum formed by protoplasmic processes of developing neuroglial cells (spongioblasts) Æ framework for growth of developing neurons in mantle layer x Stages of Neuron Formation:
1. germinal cell Æ mantle = apolar neuroblast
2. 2 processes develop from apolar neuroblast Æ bipolar neuroblast 3. one process disappears Æ unipolar neuroblast
4. remaining process extends & smaller processes dvlp on opp side Æ multipolar neuroblast 5. main process grows Æ marginal layer = axon; lengthens and either stays in CNS or grows out of CNS and becomes efferent nerve of PNS; est connections with other cell bodies or dendrites or an effector organ (ie: muscle)
6. Smaller processes of neuroblast Æ dendrites Æ ramify & est connections w/ other neurons 7. Nissl granules appear Æ neurons lose ability to divide
x Neuroglial cells also formed from germinal cells of ependymal layer
o Glioblasts Æ mantle & marginal Æ medulloblasts (spongioblasts) Æ astroblasts Æ astrocytes or oligodendroblasts Æ oligodendrocytes
x Microglia do NOT devlp frm neur tube – migrates into neural tube with BVs; mesodermal origin x Neuroblasts complete differentiation and then neuroglia are formed
x Process begins during 4th
month – not completed unto child is
x Nerve fibers become functional after they have acquired their myelin sheaths 2-3 yrs
x BVs of brain & surr CT derived from mesoderm – invade developing brain & spinal cord x Pia mater & arachnoid mater from neural crest
x Dura mater from mesoderm surrounding neural crest
x CNS Æ nerve fibers supported & ensheathed by neuroglial cells Formation of Myelin Sheath
x PNS Æ neurolemma Æ Schwann cells (from neural crest)
x Later in development, many nerve fibers of CNS & PNS develop myelin sheath o CNS Æ derived from neuroglia (oligodendrocytes)
o PNS Æ derived from Schwann cells
x Each axon invaginates cyto of Schwann cell so that it is surrounded by the Schwann cell – cell mbrn of Schwann cell also goes in = double-layered membrane Æ mesaxon
x Mesaxon elongates & spirally winds around axon, some fatty substances deposited bt layers x Unmyelinated fibers Æ no elongation of mesaxon; several fibers invaginate same Schwann cell
