Block I Flashcards
What is the scope of embryology?
Study of development of an organism from fertilization of the ovum (single cell stage) through the period of organogenesis
What is the time frame for en embryo?
Embryo: from single cell 8th week of human development = organogenesis
Fetus time frame?
Fetus: 9th week 38th week (birth)
What is organogenesis?
Where primoriums of organs starts to develop
What did karl ernst von baer (XIX) established?
Father of modern embryology:
1) Described the oocyte and cleaving zygote, blastocysts and stages of embryonic development. “established that mammals develop from eggs.”
2) Determined that general characteristics precedes specific ones: Phylotypic stage in embryonic development
father of medicine
Hippocrates
Aristotle
Founder of embryology; he thought that sperm contained a tiny human being inside.
Leonardo da Vinci
established measurements of prenatal growth
observed sperms under microscope
Anton van Leeuwenhoek
eggs come from the ovaries
regnier de Graaf
Nobel prize in Medicine 1935, primary induction [gastrulation]
Hans Spemann
Lewis, Nusslein-Volhard and Wieschaus
(Nobel prize in Medicine 1995)- discovery of genes that control embryonic development i.e., gap, pairrule, segment-polarity and homeotic genes
Describe blastocyst stage
Cell proliferation stage; first 2 weeks. from zygote to morula, blastocyst and formation of bilaminar embryonic disc.
Describe embryo stage
Weeks 3-8; constitute the dynamic period of gastrulation, folding of embryo and the formation of all the organ systems.
Describe fetal stage
Months 3-9 (full term); period of growth of all major structures that have already appeared.
Explain birth defects in the first 2 weeks
In the blastocyst period, birth defects do not originate since body systems and structures have not yet developed. teratogens usually cause the loss of the entire conceptus. spontaneous miscarriages
What is the conceptus?
embryo + placental membranes
Explain birth defects in the embryo period
Most active period of development and differentiation, thus, is the most vulnerable to mjor birth defects since teratogens interrupt development and cause birth defects
Explain birth defects in the fetal period
Birth defects in this period are usually not as severe or obvious and include small size, mental retardation, defects in the eyes, ears, teeth and external genitalia; less teratogens.
What are the first early embryonic developmental stages?
Morula
Blastula
Gastrula
neurula
WHen does the early embryonic develop. stages start?
Repeated mitotic divisions (30 hours after fertilization)
What are blastomeres?
Increased # of cells together with a decrease in size
When does the morula happen?
After the 8-cell stage, cell compaction occurs (12-32 cells = morula)
identify and what happens after this stage?
2 cell stage division;
4 stage cell division > 8 cell stage division > morula > early blastocysts > late blastocyst
What is blastocyst?
Fluid-filled space blastula or blastocyst
What is gastrula?
characterized by formation of
the 3-germ layers
Identify; what does the red circle give origin to?
PLacenta
identify
When does the morula happen?
3 days after fertilization
What is neurula?
stage in which neurulation occurs (development of nervous system) forming primarily the neural tube
What are the 3 germ layers that form in the gastrula?
ectoderm, mesoderm, endoderm
Identify
Gastrula
Where does gastrulation start?
In the dorsal/causal most posterior part of embryo with cells from mesoderm that evaginate and give origin to endoderm.
What does primitive node do?
Provide growth factors to have all tissues neede din th eembryo; Organizer = primitive knot/node (Hensen’s node in humans) Will induce the notochord
Identify
identify
iDENTIFY
what does the notochord do?
-Embryonic specific structure that defines the primordial axis of the embryo
-Defines the phylum of chordates: Urochordates and Vertebrates
-Gives some rigidity
-Is the basis of development of the axial skeleton
-Sends signals to surrounding tissue
When does the notochord disappear?
It disappears when the vertebral bodies form (4th wk)
How does the notochord transforms into as adults?
It degenerates and disappears, but it persists as the nucleus pulposus (NP) of each intervertebral disc.
What is chordoma?
tumors formed by vestigial remnants of the notochord
What are pharyngeal (branchial arches)?
Condensation of mesoderm in the cranial region will give rise to transient structures to develop vertebrate head structures. Origin of head and neck
Which cells migarate in the paharyngeal arches
mesoderm cells and neural crest cells (migrate dorsal-lateral)
What are the divisons of arch 1?
Maxillar region and mandibular region
Neural crest cells originate from?
Neural tube
Explain the neural crest cells migration
from neural tube semi open in dorsal part; when it closes in dorsal part, cells detach and migrate dorsal/lateral to form different structures including giving rise to some arches.
Mandible bones arise from?
neural crest cells that migrate to the 1st pharyngeal arch.
What structures originate from 4th - 6th arch cartilages?
-greater cornu (horn) of hyoid bone
What structures originate from Third arch cartilage?
Thyroid and cricoid cartilage
What is induction?
Process in which one group of cells or tissues causes another set of cells or tissues to change their fate.
How does induction work?
One cell type or tissue is the inducer that produces a signal, and one is the responder to the signal. It has to be a competent cell Competence- the capacity to respond to the signal (i.e., receptor expression).
What is essential for differentiation?
Crosstalk between the two cell types or tissues (induction)
How are cells in the induction period?
poorly differentiated; cells with high grade of proliferation; induction works by making these cells less proliferative and more differentiated with markers
Explain
Example: Epithelial-mesenchyme interactions
Limb mesenchyme with overlying ectoderm to produce limb outgrowth and differentiation
Primary induction-neural tube formation. Notochord induces overlying ectoderm to form neural plate (neuroectoderm).
What are some inductors that form the neural tube?
FGF-B upregulation (promotes neural plate formation
BMP-4 inhibition because promotes epidermis
Shh
Retinoic Acid
What are the types of intercellular communication?
Paracrine
Juxtacrine
cell-cell
What is the paracrine?
secreted inductor molecule; Ligand (soluble factor)/receptor (Growth & differentiation factors [GDF], morphogens) and have effect of cell that responds
What is juxtacrine?
-Receptor/membrane bound ligand in adjacent cells i.e., Notch/Delta
-Extracellular Matrix-dependent
mediated interactions by extracellular matrix or receptors in cells interacting.
What is cell-cell intercommunication?
direct contact for example: Gap junctions (connexins)
Connexins are proteins that bound cells togetehr.
What is cell differentiation?
Cells become specialized by means of cell signaling, environmental influences (secreted factors, morphogens, etc.).
What is morphogenesis?
Processes by which order is created in the developing organism.
Order is achieved through cell differentiation into tissues, organs, and the whole system.
What are the major morphogenetic processes in early embryology?
-Cell division
-Condensation
- Cell Death
- Migration
- Matrix secretion and degradation
- Growth
What do Transcription factors do?
They regulate gene expression by activating it or repressing it.
Provide examples of transcription factors
-Hox/Homeobox proteins
-Pax
-Basic Helix-loop-Helix
What do Pax proteins do?
Important for development of eye; defects here can cause ocular disorders.
What do basic helix-loop-helix do?
Regulate transcription
Where did Hox/Homeobox proteins were discovered?
first discovered in Drosophila melanogaster.
How many base pairs does hox/homeobox proteins have and what do they encode?
All the Hox genes contains 180-base-pairsequence,
the homeobox, which encodes a 60-amino-acid homeodomain composed of 3 alpha
helices.
Where does the helix bind in the hox/homoeobox proteins?
The third helix binds to DNA sites in the promoter of their target genes
what does mutations in these hox/homeobox genes lead to?
Mutations in these genes of the HOM-C complex lead to dramatic phenotypes (homeotic transformation) ie., Antennapedia gene (legs instead antennae in head)
What does defects in HOX1A lead to in humans?
impair human
neural development
Why are morphogens important?
They generate concentration gradient and send signals to aid migration, differentiation and growth factors.
What are morphogens?
Diffusible molecules that specify which cell type will be generated at a specific anatomical location
What is the function of morphogens?
Morphogens also direct the migration of cells and their processes to their final destination.
Where are morphogens found?
Many morphogens are found in concentration gradients in the embryo and expressed in opposing
gradients in the dorsoventral, anteroposterior, and mediolateral axes
By what does the fate of a specific cell is determined?
by its location along these gradients in the morphogens
What is Retinoic acid?
A morphogen derived from vitamin A and important for anteroposterior axis
What does insufficient retinoic acid lead to?
favorable caudal structures
What does high concentrations of retinoic acid promote?
cranial structures in 3’ end anterior early
Why is Retinoic acid important?
RA are powerful teratogens, especially during the first trimester.
What are hedgehogs?
Morphogens that generate concentration gradient and send signals to aid in cell differentiation pathways, migration and growth.
What morphogen was the the first mammalian ortholog of the Drosophila gene hedgehog?
Sonic hedgehog (Shh)
Mention the 3 types of hedgehog morphogens
Sonic, Indian, Desert
Where do motor neurons from nervous system originate from?
floor of neural tube
mutations in SHH or its receptor can lead to?
Holoprosencephaly- fused cerebral hemispheres is a congenital disorder linked to mutations in SHH or its receptor. When they fuse more medial.
Where is SHH secreted?
Shh is secreted at high levels by the notochord, thus providing high levels in the floor of the neural tube (promoting motor neurons
What is the primary receptor for SHH?
Patched (PTCH in human, PTC in mouse)
What can abberantly activate hedgehog signaling pathway
Some cancer types
Explain this complex
Presence of Shh- activation of signal transduction. When shh is [resent, suffers a cut and cholesterol molecule binds, inhibits and activates, they interact and the complex of SuFu with Fu can bind, the GLI get liberated and activated and with other molecules activates transcription.
Explain this complex
Absence of Shh- inactivation of signal transduction.
If there is absence of SHH, its receptor, PTCH, cannot interact with other receptor called SMO. If that interaction doesnt take place, the other complex cannot bind to SuFu (Suppressor of fused negative regulator. When that doesnt occur, the GLI transription factor modifies, goes to the nucleus and inhibits gene expression.
what is TGF-B?
Transforming Growth Factor ℬ a morphogen important for the migration and axonal guidance.
Why is TGF-B important?
TGF-ℬ signaling is a tumor suppressor factor and inhibits cell proliferation. Its dysregulation has been implicated in cancer
Explain the comoplex
In absence of TGF, TBR-II is phosphorilated, so phosphorilation of TBR-II doesnt occur and phosphorilation of trasncription complexes dont occur either; they dont go to the nucleus thius no gene expression.
On the other hand, if TBR-II phosphorilates TBR-I, it phosphorilates R-Smad complexes which are transcription factors that can pass to the nucleus and activate gene expression.
What is Receptor tyrosine kinases (RTK)?
group of membrane-bound receptors that play an important role in the normal function of cells by
phosphorylating tyrosine residues on intracellular substrate proteins
How do TGF-B work?
TGF-B binds to transmembrane kinase receptors (RTK) to phosphorylate intracellular receptor-associated
Smad proteins (R-Smads). Smads complexes regulate target gene expression in the nucleus
What is fibroblast growth factor and some of its roles? (FGF)
A morphogen that Influences morphogenesis in embryonic development. Some of its roles include: cell migration, differentiation, survival, apoptosis, induction, among others and may form a concentration gradient over the developing embryo.
How was FGF discovered?
Discovered by its role in stimulating cell growth and proliferation of mouse fibroblasts
How many receptors does FGF have?
four isoforms FGFR1-R4
Tyrosine kinases can phosphorylate in?
Tyrosine residues
What do heparan sulfate proteogylcans do?
(in extracellular matrix) modulate FGF diffusion and gradient formation
In what embryological development is FGF important?
When formation of capillaries and blood vessels start to form/
What is Wnt/b - catenin pathway>
allow catenins inside the cell to go to the nucleus and activate, along with a transcription factor, gene expression.
Explain the pathway
Wnt can interact with its receptor Fzd and also with the co-receptor LRP5/6. This promotes the complex that B-catenin doesnt phosphorylate making B-catenin accumulate in the cell and goes to the nucleus to activate geen expression.
On the other hand, in Wnt absence, there is no interaction of receptor with co-receptor and all the trabscription factors pomote B0catenin to phospjhorylate with the promotion of an enzyme, the signal is to degrade b-CATENIN; Thus, it cannot bind to TCF factor and since TCF factor is a suppressor and needs catenin to activate transcription, it suppresses the expression.
What does Wnt direct?
Wnts direct cell polarity, proliferation, apoptosis, cell fate and morphogenesis (patterning the CNS, the gut,
the respiratory and circulatory systems, among others
What cancer does Wnt promote?
Also play role in tumor formation (colorectal cancer in humans)
Is notch delta signaling pathway a morphogen?
No
In what does notch delta signaling pathway depend?
cell-cell interaction, cell with receptor notch and other cell with ligand delta/jagged
Explain pathway
Notch/Delta Signaling Pathway
Ligand-receptor interaction triggers proteolytic events leading to the release of the Notch Intracellular domain (NICD). NICD translocates to the nucleus for activation of the transcriptional complex, activating target genes that inhibit proliferation, and thus
maintaining the progenitor state of the cells.
Activates genes that inhibit differentiation leave cells in pluripotent stage, this is called lateral inhibition.
What is the notch delta pathway important for?
This pathway is integral for cell fate determination, maintenance of stem-cell niches (lateral inhibition), apoptosis, and differentiation
What are notch proteins?
Notch proteins are single transmembrane receptors that interact with membrane-bound Notch ligands (i.e., Delta/Jagged) on adjacent cells
What are cadherins?
Cell Adhesion Molecules; (calcium-dependent adhesion)
In what are cadherins involved?
cell recognition, signaling, communication, morphogenesis, angiogenesis,
whY are cadherins important?
They attach to each other and create stiffness and strong tissues due to anchorage.
What is Epithelial-Messenchymal transition (EMTs)
Acquisition of mesenchymal features from epithelial cells and occurs in gastrulation during normal embryonic development for mesoderm, notochord etc. Also seen in adult tissue regeneration
What happens if theres a disregulation in EMTs?
Cancer progression.
EMT allows solid tumors to become more malignant, invasive & metastatic.
Histologic features connecting secondary metastatic tumors to the primary is called mesenchymal epithelial transition (EMT).
Cadherins are important markers for the expression of EMT (others are TFs and enzymes [MMPs])
What is Messenchymal-Epithelial transition (METs)?
Metastatic tumor cells at distant sites undergo MET (may be found at different transition stages).
§ Mixed expression of epithelial and mesenchymal markers
§ EMT or MET modulation is an important approach to avoid metastasis
What is epigenetics?
inherited changes that affect egen expression as a result of modification to the DNA but not to the sequence, by methylation or acetylation
what is methylation and hypomethylation?
methylation:
add methyl groups at cytosine residues which results in reduction of gene expression (silencing) by prohibiting transcription factors by going into the promoter.
Hypomethylation: poor methylation, gene more open to promoter area so that transcription factors can enter, resulting in gene over expression.
what is acetylation?
add acetyl groups to histones (proteins around which DNA is coiled). Acetylated DNA is less tightly bound to histones = more open access for transcription
How is embryonic age calculated?
It is difficult to determine exactly when fertilization(conception) occurs because the process cannot be observed in vivo (within the living body). Physicians calculate the age of the embryo from the first day of the last normal menstrual period (LNMP). This is the gestational age, which is about two weeks longer than the fertilization age because the
oocyte is not fertilized until about two weeks after the preceding menstruation.”
When does gestational age begin?
During the day 1 of last menstrual cycle. Last normal menstrual period (LNMP)= gestational age, which is
two weeks longer than the fertilization age.
What are stages in embryonic age calculation?
Stages during early embryonic development begin at fertilization.
What happens in stage 1?
fertilization
What happens in stage 2?
Zygote divided and morula appears
What happens in stage 3?
Early and late blastocyst form
What happens in stage 4?
Implantation begins
What are totipotent cells?
Cells in Zygote and early morula capable of differentiate into any cell type. Ethical issues.
What are Embryonic stem cells (ES)
are derived from the inner cell mass of the embryo (blastocyst) and are pluripotent.
What are pluripotent cells?
these cells have lost the capability of differentiating like totipotent but can form virtually any cell or tissue type, they have the potential of curing a variety of diseases, including diabetes, Alzheimer and Parkinson diseases, anemias, spinal cord injuries, and many others. Ethical issues.
What are Adult stem cells?
Adult tissues contain stem cells that may also prove valuable in treating diseases. These cells are restricted in their ability to form different cell types and, therefore, are multipotent, not pluripotent… Less ethical issues
Where are gametes derived from?
Derived from Primordial Germ Cells (PGCs)
Where are PGCs found?
during 2nd week in the wall of yolk sac
what is the main function of the yolk sac?
provide nutrients and transfers nutrients to embryo, since embryo at the beginning is not connected to placenta.
Where do PGCs come from?
-PGC’s come from the ectoderm (posterior part
of primitive streak IN CAUDAL/DORSAL PART).
-Then cells migrate to the endoderm, allantois, and
wall of yolk sac.
-Cells undergo mitosis (proliferation)
Where and when do PGCs migrate to?
PGCs migration to the developing gonads (genital ridge) during the 4th week to the genital ridge which is the primordium of gonad
What is Spermatogenesis?
is the process of producing sperm with half the number of chromosomes (haploid). The germ cells progress from the diploid to haploid state and then change their shape to become spermatozoa.
where does gametogenesis (spermatogenesis) take place?
In the seminiferous tubules
In what phases is male gametogenesis divided?
- Spermatogenesis
- Meiosis
- Spermiogenesis
What happens in spermatogenesis?
- PGCs (46;2N) in the testes remain dormant until puberty. At puberty, these cells differentiate into type A spermatogonia (46, 2N; initiation of spermatogenesis). Less differentiate stage.
- Type A spermatogonia undergo mitosis (spermatocytogenesis) to maintain a continuous supply of stem cells throughout the reproductive life of the male. Type B spermatogonia (46;2N) produces after the last division of Type A cells.
What happens in meiosis?
- Type B spermatogonia divide to form primary spermatocytes 46;4N (not meiosis)
- Primary spermatocytes complete meiosis I and produce two secondary spermatocytes
(23;2N) - Secondary spermatocytes complete meiosis
II to form four spermatids (23;1N)
What happens in spermiogenesis?
- Series of changes that transform spermatids
into spermatozoa - Includes acrosome formation,, nucleus condensation, formation of the head, neck and tail
~ 74 days from spermatogonia to spermatids
~ 300 millions sperm cells/day
Cytokinesis is incomplete-cytoplasmic
bridge
What is an acrosome?
acrosome (important organelle for fertilization) which covers half of the nuclear surface and contain enzymes to assist in penetration of the egg
Identify
What stertoli cells, where are they located and their function?
surround spermatogonia and spermatids in the gonads.
They are located in the basement membrane of the seminiferous tubules.
They provide nutrients, support, as well as protection
How to stertoli cells work?
Sertoli cells respond to Follicle Stimulating Hormone
(FSH)-for synthesis of androgen receptor [important for leydig cells that produce testosterone so if there is testosteroe, the sertoli cells can respond to the receptor]
Androgens binds to Sertoli cells to promote
spermatogenesis
Release from the Sertoli cell = spermiation
(determinant for sperm count in the ejaculate) basically liberated the sperm
From what does sertoli cells derive?
Interstitial cells
What do leydig cells respond to?
Respond to Luteneizing Hormone (LH) produced by pituitary glad, to produce testosterone
Where are leydig cells located and how do they change?
Found between seminiferous tubules-close to blood vessels.
Fetal Leydig cells degenerate after birth, but during
puberty, Leydig cells re-differentiate from connective tissue
Are spermatozoa motile?
Spermatozoa are nonmotile during storage in the epididymis, but become motile in the ejaculate.
What is female gametogenesis?
Oogenesis;
PGCs (46;2N) migrate to the developing gonads (ovaries) during the 4th week.
Once in the gonads, germ cells differentiate into
oogonia
Where does the blastocyst implant?
Edometrium
Where does fecundation occur?
ampulla
What happens when primary oocyte enters prophase I?
Some enter meiosis I and arrested in prophase I
What happens to the female fetus in the womb at 4 months old?
Oogonia in clusters in the cortical part of the ovary
What happens to the female fetus in the womb at 7 months old?
All oogonia transformed to primary oocytes
What happens to the female newborn?
No oogonia present
No more primary oocyte formation after birth and arrested in prophase I until ovulation
what are the Flat epithelial cells in a newborn female?
secrete oocyte maturation inhibitor factor (OMI)
how many primary oocytes remain from birth to puberty?
40,000
From 40,000 primary oocytes present til puberty, how many become secondary oocytes?
400 will become secondary oocytes and ovulated
What is the zona pellucida?
-sulfated glycoprotein material secreted by epithelial cells and the oocyte
-mediates initial sperm-egg recognition and induces the acrosome reaction in spermatozoa
-Surrounds the developing embryo until the blastocyst stage (protection in the oviduct)
what are granulosa cells?
cuboidal folicular cells startified and modified more protection
primary follicle is said to be?
pre-antral
What is the secondary follicle referred to and why?
Antral, due to fluid accumulation, appearance of antrum cavity and accumulation of cells surrounding the secondary oocyte called Cumulus oophus.
What is the theca interna?
connective tissue that provide steroid precursors to
the granulosa cells for them been able to produce estrogen.
Mature secondary follicle (Graffian) is________
preovulatory follicle ~25mm diameter; 37 hours before ovulation
When does meiosis I completes in adolescence?
-Shortly before ovulation, 1ry oocyte completes meiosis I (secondary oocyte)
When does meiosis II start?
When a release of LH is activated and ovulation starts
Meiosis II is completed only if ________
the oocyte is fertilized, If not, it degenerates.
Meisosis I is completed when?
When primary oocyte differentiates and is arrested in prophase I just before ovulation
What is the stigma?
bulge in the wall of the ovary so that oocyte is liberated
Where does the corona radiata originate from?
The cumulus oophorus cells rearrange around the
zona pellucida to form the corona radiata
What is the corpus luteum?
Cells from the follicle and theca interna forms the
corpus luteum and secrete progesterone (in case that
fertilization occurs). This causes the endometrium to enlarge for protection and proliferation of conception
What are the layers of the endometrium?
Compact layer and spongy layer
What is the GnRH?
Gonadotropin releasing hormones acts on the pituitary and pituitary produces FSH and LH; FSH matures the folicle and estrogen produced by epithelial cells enlarge the endometrium then the egg is liberated in ovulation by LH.
When does fertilization occur?
(12-24 hours after ovulation)
What happens to corpus luteum if fertilization doesnt occur?
(degenerated corpus luteum = corpus albicans)
When does the placenta take over hormonal production?
20th week of pregnancy
What is a zygote?
Fusion of mature male and female gametes (restoration of diploid number 2N)
What is Sperm Maturation (capacitation) before Fertilization?
Capacitation is a period of conditioning in the female
reproductive tract (~7 hours) that allow removal of glycoprotein coat and seminal proteins from the
plasma membrane that overlies the acrosomal region of the sperm.
Describe the phases of oocyte penetration
phase 1 Spermatozoa pass through the
corona radiata barrirer (hyaluronidase dependent
phase 2. permatozoa penetrates the zona
pellucida. enzymes released from the acrosome ie.,
esterases, acrosin. This is known as the acrosome reaction. digestion of zona pellucida, reuquires a lot of energy
phase 3. Spermatozoa penetrates the oocyte
membrane while loosing its own plasma membrane. This elicits a zone reaction that makes the zona pellucida impermeable to other sperms.
How long does it take to sperm to reach the oviduct?
2-7 hours from the cervix to oviduct.
Where does the zone reaction come from?
believed to result from the action of lysosomal enzymes released by cortical granules near the plasma membrane of the oocyte.
Identify
Male and female pronuclei (Ootid)
Two-cell stage zygote
Where can teratomas occur?
They may occur in both gonadal and extragonadal tissues
What are teratomas?
PGCs that have strayed from their normal migratory pathway
-Ovarian, testicular, sacrococcygeal, mediastinal, buccopharyngeal tumors mostly benign, highly vascular
Mention some chromosomal abnormalities
§ Trisomy 21 (Down syndrome)
§ Klinefelter syndrome
§ Turner syndrome (X0)
§ Trisomy 13
§ Trisomy 18
Mention some Prenatal Predictors of Chromosomal Abnormalities
-absence or hypoplasia is a predictor of Down’s Syndrome
Increased nuchal thickness (translucency)
Turner’s syndrome (XO)
Down syndrome (Trisomy 21)
Explain abnormal gameets
Usually degenerates or die before reaching maturity
10% of all spermatozoa
Less motile and do not fertilize oocytes
What is a normal sperm count?
Normally- more than 100 million sperms/ml semen
What is the importance of motility of sperm?
The motility of sperms is very important, 40% of sperms should be motile after 2 hours and some should be motile after 24 hours.
What is the sperm count of sterile men?
10 million sperms/ml semen, likely to be sterile.
WHy does male infertility happen?
Male infertility might take place by endocrine disorders, abnormal spermatogenesis, or obstruction of a genital duct such as the ductus deferens
What is anovulation?
-absent ovulation elicited by inadequate release of gonadotropins
-unable to become pregnant
What is the recommendations for anovulation and its disadvantages?
administrate gonadotropins or an ovulatory agent such as clomiphene citrate (stimulates the release of FSH and LH)
disadvantages: multiple pregnancy increases up to ten-fold when ovulation is induced
what are some forms of birth control?
-Vasectomy
-contraceptive pill
-barrier techniques (Condom, diaphragm, cervical cap)
-RU-486 (mifepristone)
-Plan B
-Male pill in clinical trials
What is the vasectomy?
deferentectomy) in the male consists of excision of a segment of each ductus deferens.
How does the contraceptive pill work?
combines estrogen and progesterone for inhibition of
ovulation. Prevents the release of FSH and LH.
How does RU-486 (Mifepristine) work?
Causes abortion (abortion pill). It is an antiprogesterone drug. The uterine lining starts to shed. The cervix softens and bleeding occurs.
how does the morning after pill (plan b) work?
Prevention after intercourse, giving a short-high burst of synthetic hormones. Best when used during the first 24 hours. Inhibits ovulation and follicle rupture. Not an abortion pill
how do the male pill BC works?
Inhibits FSH and LH release. Stops or lower testosterone levels and sperm production to a level of infertility
What is the pre-embryonic period?
embryonic: Weeks 1 and 2 (fertilization, cleavage, morula, blastocyst, formation and implantation)
What is the embryonic period?
Embryonic: Weeks 3 8 (gastrulation starts in week 3)
What happens after the 8-cell stage?
cell stage, cell compaction occurs (12-32 cells = morula)
when do repeated mitotic divisions happen?
(30 hours after fertilization)
WHat are blastomeres?
Increased # of cells together with a decrease in size = blastomeres)
When does morula occur?
3 days after fertilization
What happens on days 4-5 approx?
Fluid filled space appears = blastocystic cavity or blastocoele in early blastocyst) and separates the blastomeres in two parts:
-outer cell layer trophoblast= embryonic placenta)
-inner cell mass primordium of the embryo (embryoblast)
Whe deos morula enter the uterus?
4 days after fertilization
When does zona pellucida degenerate?
2 days after blastocyst reaches uterus
How does zona pellucida degenerate?
Trophoblast releases degradative enzymes that break down the zona pellucida
When does the trophoblast adhere to the edometrium epithelium of the mother?
Day 6
In what day does the trophoblast divides into which cells?
Day 7;
cytotrophoblast (mitotic mononuclear cells)
syncytiotrophoblast (multinucleated protoplasmic mass in which no cell boundaries can be observed, no se dividen)
How does the first week of implantation end?
With the implantation of blastocyst and differentiation of cells destined to be a placenta.
When does Syncytiotrophoblast cells invade the endometrium?
Day 8
What is the function of the syncytiotrophoblast?
to anchor the blastocyst into the wall of the uterus
Embryoblast divides into:
Epiblast (primary ectoderm)
Hypoblast (primary endoderm)
What is the component of epiblast and hypoblast called?
embryonic disc
What is the decidual reaction and when does it happen?
During the 8 week and is when cells near the syncytiotrophoblast (decidual cells of uterus) start to grow due to glycogen and lipids; and then degenerate to provide nutrients by getting engulfed by the syncytiotrophoblast for rich source of embryonic nutrition
how si the endometrial connective tissue called?
stroma
Whta is the immuno privileged site for the conceptus [ embryo + placenta])?
cells adjacent to the implantation site (decidual cells of the uterus
hOW DOES AMNION FORM?
From the migration of some epiblast cells called amnioblast, to contribute to form a thin membrane (amnion)
What is the amniotic cavity?
Space formed between the epiblast and amnion and where the embryo will be developing
What is the exocoelomic membrane and when does it happen?
Also called Heuser’s membrane; is the formation of the migration of hypoblast (primary endoderm) cells. It takes place during 9-10 days after implantation
What lies between the hypoblast and the exocelomic membrane?
The exocelomic cavity or primitive yolk sac or primary umbillical vesicle
The blastocyst cavity transforms into?
the exocelomic cavity
Why is the yolk sac important?
important for early nutrition of the embryo (2- 3 weeks).
bY WHAT WILL THE HYPOBLAST (PRIMARY ENDODERM) WILL BE REPLACED BY?
Definitive endoderm
What is the lacunar stage and when does it happen?
cells in syncytiotrophoblast will fuse and migrate and form spaces called lavunae (trophoblastic) and are vacuoles for receiving nutrients of the mother by difussion from her blood vessels into the embryo. This happens during day 9-10 approx.
The blastocysts is closed by?
a fibrin coagulum inside the endometrium
What are susoids and why are they important?
Are the capillaries of the mother that fuse into the lacunae to provide nutrient (fluid-embyotroph) to the embryonic disc by fussion. Form by 11-12 days
What is the primaty uteroplacental circulation?
Fusion of the syncytial lacunae and sinusoids (maternal capilaries)
What hormone produces the syncytiotrophoblast and what does it do?
hCG Human chorionic gonadotropin hormone. Enters the maternal blood in the lacunae and maintains the development of spiral arteries in the myometrium and formation of syncytitrophoblast.
When is hCG detectable?
at the end of the second week (day 9-10)
What does hCG support?
supports the corpus luteum and thus maintains the supply of progesterone for the first trimester
What tissue develops in the day 12?
As soon as the 1 ry yolk sac forms, a new population of cells (extraembryonic mesoderm) appears between the Heuser’s membrane (exocelomic membrane) and the cytotrophoblast. is primarily derived from the hypoblast, with contribution of the epiblast and the cytotrophoblasts.
What are the vacoules between the extraembryonic somatic mesoderm and exocelomic membrane?
extraembryonic cavity (coelom) or chorionic cavity
In what is the extraembryonic mesoderm divided?
-Lining covering the yolk sac = Extraembryonic splanchnopleuric (splanchnic or visceral) mesoderm
-Lining covering the cytotrophoblast and amnion = Extraembryonic somatopleuric (somatic) mesoderm
What happens in day 13?
Vacuoles (extraembyonic cavity) fuse forming the chorionic cavity and and the primary yolk sac decrease in size forming the secondary yolk sac or definitive yolk sac and at the bottom remains the exocelomic cyst or remnant of primary yolk sac
What is the chorionic plate?
fetal part of placenta (extrae,bryonic somatic mesoderm) lining adjacent the inside of the cytotrophoblast and gives rise to chorionic villi.
What is the connecting stalk?
(thick stalk of mesoderm) present after development of blood vessels= umbilical cord. Comes from mesoderm and forms in day 13
What is the chorionic villi?
day 13 only primary villi; First step for development of chorionic villi = presence of primary villi (cytotrophoblasts proliferation inside the syncytiotrophoblast only two types of cells. For gas exchange
Describe yolk sac
The secondary yolk sac is formed by splanchnopleure
(extraembryonic [visceral] mesoderm) plus a layer of
endoderm. It is the initial site of hematopoiesis in the
conceptus during development. Also important in
nutrition by absorbing fluids from the exocoelom.
Describe allantois
Formed by splanchnopleure plus endoderm derived from the caudo ventral portion of the secondary yolk sac. The allantois is rudimentary in the human and higher primates, but is large and well developed in many other mammals. The body stalk and the associated umbilical vessels are undoubtedly derived from allantoic mesoderm.
Describe Amnion
Formed by somatopleure (extraembryonic somatic
mesoderm) plus a thin layer of extra embryonic ectoderm (amnioblasts). The amnion is a fluid filled sac surrounding the fetus and providing an aqueous environment in which the fetus can grow free from distortion.
Describe chorion
Formed by somatopleure plus a layer of trophoblast
(cytotrophoblast and syncytiotrophoblast)
What forms the chorion?
The extraembryonic somatic mesoderm and the two layers of trophoblast (cytotrophoblast and syncytiotrophoblast form the chorion which forms the wall of the chorionic sac (where the embryo is suspended)
Identify
Identify
Identify
Identify
What does trophoblast divide into?
syncytiotrophoblast and cytotrophoblast week 2
What does embryoblast divide into?
Epiblast & hypoblast week 2
What does extraembryonic mesoderm divide into?
Splachnid & somatopleuric week 2
What is the main event in week 3?
Gastrulation (morphogenesis)
What is gastrulation?
establishes the 3 germ layers of the embryo: ectoderm, mesoderm and endoderm and determines the axis of embryo
What is the primitive streaK?
by the end of week 2 - thickened linear band of epiblast that appears caudally in the dorsal and caudal aspect of the embryo It includes the groove, pit and node. PS
establishes cranio caudal, dorso ventral and right left sides
what happens in day 16?
epiblast migration of FGF-8 & BMPs dependent- epiblast cells detach and form: Definitive endoderm, mesoderm and ectoderm which are remaining epiblast cells
what does the cranial end of primitive streak form?
primitive node
What is the organizer of the embryo?
priitive node
Hypoblast gives rise to?
endoderm of yolk sac and extraembryonic mesoderm
The cells closer to cranial region of prechordal plate change to more columnar cells for what?
Give rise to cranial structures like eyes
What morphogens activate in the precordal plate for endoderm of oropharyngeal membrane?
Shh and PAX6.
What are the derivatives of the embryonic ectoderm?
epidermis, CNS, PNS, retina of the eye
What are the derivatives of the embryonic endoderm?
epithelial linings of respiratory tract and GI,
glandular cells of the GI, urinary bladder
What are the derivatives of the embryonic mesoderm?
smooth & striated muscle, connective tissue, most
of the cardiovascular system, blood cells and bone marrow, skeleton, reproductive & excretory organs.
What is the gastrula?
Embryo composed of 3 germinal layers (trilaminar embryonic disc)
What is the main function of notochord?
Defines the primordial axis of the embryo
Gives some rigidity
Is the basis of development of the axial skeleton
Important for neural induction
What happens to notochord in week 4?
It degenerates and disappears when the vertebral bodies form but persists as nucleus pulpous NP of each intervertebral disc
Where does notochord originate and its location?
It extends from the oropharyngeal membrane to the primitive node and comes from mesodermal cells
What are clinical correlations of notochord?
if these pluripotent cells remains they can form a chordoma which is a tumor formed by the vestigial remnants of the notochord.
What is the notochordal process?
Some mesenchymal cells migrate cranially from the primitive node and pit forming a median cellular
cord. mesoderm origin.
How does the notochordal process transforms?
floor fo notochord along with primary endoderm will start to degenerate and disappear and the neuroenteric canal arises. The evagination of the roof unites with the mesoderm that was near
What does the notochord roof and neural groove give rise to?
future central nervous system, ectoderm derived
Where does notochord floor come from?
Embryonic endoderm
Where do notochord walls come from?
mesoderm
What is the allantois and when does it form?
Appears ~ (E 16) as a small diverticulum (protrusion) from the caudal wall of the yolk sac. (3rd week
What is the importance of the allantois?
Small in human embryos (exchange of liquid waste and gases). In the 2nd month it ceases to grow, and then is obliterated. Involved in early blood formation and is associated with the development of the
urinary bladder.
IN what does the blood vessels of the allantois turn to?
umbilical arteries and vein and its fucntions are taken over by placenta and amniotic sac
When bladder enlarges in what does the allantois transfor to?
urachus, median umbilical ligament
How does chorionic villi develop into secondary and tertiary villi?
Mesenchyme grows into the primary villi = secondary
chorionic villi and as mesoderm evaginates, gives rise to the tertiary villi
What does the outer cytotrophoblast do?
Attaches villi to the endometrium, anchors chorion.
what is the intervillous space?
Lacunae of mother
Chorionic plate is composed of?
mesoderm attached to cytotrophoblast
what is Arteriocapillary network and how does it form?
fused capillaries in chorionic villi (become connected with the primordial heart through vessels that differentiate in the mesenchyme of the chorion and
connecting stalk)
WHat happens by the end of 3rd week?
Embryonic blood flows through capillaries in the chorionic villi tertiary becasue they have blood vessels.
-Oxygen and nutrients in maternal blood diffuse through the wall of the villi and then enter the embryo’s blood products diffuse from
embryonic blood to maternal blood
What is the hyadatidiform mole?
molar pregnancy; an abnormal placental tissue and type of gestational trophoblastic disease (GTD); characterized by trophoblastic tissue but no embryo cells or small number of embryo cells. Moles secrete hCG thus mimics pregnancy.
these moles are aborted in early ppregnancy
What is the treatment for hydatidiform mole?
UTERUS SHOULD BE EVACUATED BY CERVIX DILATION AND CURETAGGE
Identify
Hydatidiform mole
What is a risk of the hydatidiform mole?
can develop into a choriocarcinoma is cells remain and proliferaate and is a gestational trophoblastic neoplasia
What is the treatment for choriocarcinoma?
Chemotherapy and hysterectomy and it can mestatisize into lung or brain
Describe partial mole
Embryonic tissue or amniotic sac is present
Swelling of the villi is focal
Malignancy rare
Ovum is fertilized by 2 sperms (69chromosomes)
describe complete mole
Embryonic tissue is absent
Swelling of the villi is difusse
Malignancy 5 10%
Anucleated ovum is fertilized by a sperm that will duplicate (46 chromosomes of paternal
origin only)
What is sacrococcygeal teratomas?
Remnants of the primitive streak (pluripotent cells) may persist and give rise to a tumor (but can arise
also from PGCs)
*Tumor contains derivatives of the 3 germ layers
*Most common tumor in fetus and newborns 1:35,000
*Most are benign (potential to be malignant), 80% in females (4:1)
what is the diagnosis of sacrococcygeal teratomas
- Prenatal ultrasound exam test
*High blood levels of alpha fetoprotein (AFP) between weeks 16 -20) - Mother’s uterus is larger than it should be
- Treatment usually surgical excised (through perineum or abdomen) with good prognosis
- Might require coccyx resection
What is Caudal dysgenesis?
Sirenomelia, is a defect in gastrulation; Mesoderm deficient in the caudal most region of the embryo.
Decreased blood flow to the caudal regions, in combination to abnormal mesoderm development
are the main might cause the Caudal Regression Syndrome (CRS)
*
Defects hypoplasia and fusion of the lower limbs, anomalies of the genital organs, renal agenesis or urination difficulties, vertebral and genital organs abnormalities, imperforate anus
What is the diagnosis of sirenomelia, prognosis and risk factors?
Diagnosis prenatal ultrasound , genetic testing
*
Prognosis there is no cure, but treatment is offered to correct abnormalities Mild condition have better quality of lives If severe, poor prognosis and many
newborns may die
*
Risk factors maternal diabetes and genetic and environmental factors
*
In mice: abnormal expression of genes Brachyury, WNT, engrailed
identify
Sacrococcygeal teratomas
identify
Sirenomelia
What is the conceptus?
The embryo and its adnexa; associated membranes ie., amnion, chorion, yolk sac). It includes all embryonic and extraembryonic structures
What is the main function and metabolism of placenta?
Synthesizes: glycogen, cholesterol, fatty acids and proteins
function: provides nutrients and energy
What are some molecules that pass through the membrane?
-oxygen, carbon dioxide, carbon monoxide, water, glucose, vitamins
-hormones, mainly steroids
-electrolytes
-maternal antibodies (most IgG)- passive immunity
-waste products (urea, uric acid, bilirubin)
-drugs and their metabolites
fetal drug addiction
Some antibiotics
-infectious agents
cytomegalovirus (family of herpes virus), rubella
(“sarampión alemán”), measles (““sarampión), varicella,
poliomyelitis… Microorganisms such as, Toxoplasma gondii
(parasite) and Treponema pallidum (syphilis)
How do molecules pass from placenta?
by difussion, active transport and pinicytosis.
what is the endocrine function of hCG?
Secreted by syncytiotrophoblast,
-supports corpus luteum
what is the endocrine function of Human chorionic somatommotropin (hCS) or lactogen (hPL)?
stimulate mammary development and energy supply
what is the endocrine function of Human chorionic thyrotropin (hCT)?
placental derived hormone equivalent to TSH
what is the endocrine function of Human chorionic corticotropin (hCACTH) (hCT)?
equivalent to corticotropin (ACTH) from the pituitary
what is the endocrine function of progesterone and estrogen?
-support maternal endometrium
-estrogen from the syncytiotrophoblast
-by 4th month these hormones maintain pregnancy without the corpus luteum
what si the chorion frondosum?
where primary, secondary and tertiary villi are rpesent, closer to the embryo (cranial part)
what si the chorion smooth (leave)?
Less villi due to the pole (aembryonic pole: no EMBRYO close)
Identify
What is the decidua?
Gravid endometrium- functional layer of the endometrium in a pregnant woman. It separates from the remainder of the uterus after parturation.
What is the decidua basalis?
deep to the conceptus, forms maternal part of
the placenta
What is the decidua capsularis?
capsularis-superficial part of the decidua, overlying
the conceptus
What is the decidua parietalis?
remaining part of the decidua
Identify
Which decidua degenerates?
capsularis
When tha amniotic cavity fuses with chorion how is it called and when does it happen?
Amniochorionic membrane, fused at end of 3rd month
What structure ruptures and it is said that “rompió fuente”?
Aniochorionic membrane
How does the maternal side of the placenta look and called?
derived from endometrium
-Cotyledons (15-20)- contains stem villi and their branches
-form cobblestone appearance
-originally placental septa formed grooves
-covered with maternal decidua basalis
How does the fetal side of the placenta look and called?
developed from chorionic sac
(villous chorion)
-umbilical cord attachment
-cord 1-2 cm diameter, 30-90cm long
-covered with amniotic cells
what is inside the villi?
Main stem villus and branch villus (capillaries)
How is the memebrane of placenta before the 20th week?
4 layers: syncytiotrophoblast, cytotrophoblast, edothelium and conncective tissue
How is the memebrane of placenta after the 20th week?
cytotrophoblast absent (3 layers): syncytiotrophoblast, mesoderm, endothelium, only remaining cells for gas and nutrient exchange
identofy
How are arteries and veins arranged in the placenta?
Theres ONE big vein that is rich in Os and 2 umbilical arteries that are poor in O2and bring the “desechos” of the fetus. Umbilical vein supplies oxugenated blood to fetus.
What is hemolytic disease of newborn (HDN)?
Hemolysis of fetal Rh-positive blood cells and anemia
(erythroblastosis fetalis). Anemia causes fetal hydrops
(edema and effusions into the body cavities and fetal death)
Because small amounts of fetal blood cells pass to the maternal circulation through microscopic breaks in the placental membrane
*If the fetus is Rh positive and the mother is Rh negative, the fetal cells stimulate the formation of anti-Rh antibody by the immune system of the mother
What is the treatment to prevent hemolytic disease of newborn?
Special immune globulins, called RhoGAM, are now used to prevent this sensitization around the 28th week of pregnancy and again within 72 hours after the delivery of an Rh+ baby. This must be done for the first and all subsequent pregnancies. The serum provides only a passive form of immunization and will shortly leave her blood stream. Therefore, she does not produce any long-lasting antibodies.
*Homozygous dominant (DD) or heterozygous (Dd) are Rh+. Those who are homozygous recessive (dd) are Rh- (i.e., they do not have the key Rh antigens).
Describe the blood flow through embryo
Maternal Blood | > umbilical vein -> liver -> anastomosis -> sinus venosus -> atria ventricles-> truncus arteriosus -> aortic sac -> aortic arches-> dorsal aorta-> pair of umbilical arteries | Maternal blood
Identify
What does the umbilical cord do?
The umbilical cord protects the fetal vessels that connect the placenta and fetus
-Cord 1-2 cm diameter, 30-90 cm long
What is fetal anoxia?
Long cords might coil around the body of the fetus
What surrounds the 2 arteries and vein of umbilical cord?
Wharton jelly (mucoid connective tissue)
What happens in the velamentous insertion of umbilical cord?
The cord is attached to the amnion and chorion, not to the placenta. The umbilical vessels leave the cord and run between the fetal membranes before spreading over the placenta. High risk of vessels being ruptured during normal delivery or when Vasa Previa is diagnosed. C-section recommended.
what is vasa previa?
when the umbilical vessels cross over the inferior uterine segment (cervix). Might cause vaginal bleeding & fetal bradycardia or death)
What is umbilical cord prolapse?
The umbilical cord comes out before the fetus, can cause problems due to pressure.
What happens if there is an absence of umbilical artery?
-Usually not of clinical significance
-Increased incidence in twin pregnancies
-Associated with cardiovascular disease and other chromosomal and fetal abnormalities
-Remaining artery usually as large as vein
- ~1 in 200 newborns
The umbilical cord is rich in what?
Stem cells, can be used for bone marrow transplant for leukemia, due to pluripotent cells.
Where does amniotic fluid come from?
derived from maternal tissue fluid by diffusion across the amniochorionic membrane from the decidua parietalis. Also from diffusion of fluid from blood through the chorionic plate, respiratory tract and urine (11th week). -Before keratinization of the skin, amniotic fluid is similar to fetal tissue fluid
How many mL of amniotic fluid does a fetus ingest?
~400 daily
What are the functions of the amniotic fluid?
-Permits symmetrical external growth
-Barrier to infections
-Permits normal fetal lung development
-Cushions the embryo
-Maintains fetal body temperature
-Free movements
-Prevents adherence of the amnion to the embryo
what happens if there is low volume of amniotic fluid?
Oligohydramnios; (risk of cord compression, musculoeskeletal abnormalities, restriction of growth). Caused by fetal urinary tract abnormalities, genitourinary obstruction, uteroplacental insufficiency, dehydration of the mother.
what happens if there is high volume of amniotic fluid?
Polyhydramnios- high volume of amniotic fluid (risk of: cord prolapse, placental abruption, premature birth, anencephaly, perinatal death). Caused by maternal diabetes , or in the fetus, by high polyuria and defects in swallowing.
what is the amniotic band syndrome? (ABS)
Caused by premature rupture of the membranes (amnion) Constriction of limbs, digits… Prenatal ultrasound diagnosis of ABS
Identify
ABS
What is the placenta previa, percreta and accreta?
previa is in the internal os of uterus can cause hemorrage, delivery by cesarean.
accreta and percreta- trophoblast rgowns into endometrium and can cause hemorrage
beningn od pre-malign GTD
Complete Hydatidiform Mole and partial hydatidiform mole; but can turn into choriocarcinoma which is malignant
malignant disorders of placenta
Gestational Trophoblastic Neoplasia (GTN) ie.,
choriocarcinoma. Usually preceded by a mole.
Differs from PSTT both morphologically and biologically
Placental-Site Trophoblastic Tumor (PSTT)
Occurs after pregnancy. This is a rare slow growing tumor that develops where the placenta attaches to the uterine wall (usually the myometrium). Presents at early age and hCG is lower than in choriocarcinoma. Usually curable.
Identify
Identify
What is preeclampsia?
Condition characterized by maternal hypertension, proteinuria (protein in urine) and edema
*It may begin anytime from 20 weeks’ gestation
*May result in fetal growth retardation, fetal and/or mother deaths
*Cause not well known, could be due to incomplete differentiation of cytotrophoblast cells (vascular problems)
*Higher incidence in women with diabetes and those with smoking habits
*May develop into eclampsia (convulsions and possible miscarriage and maternal death
1st labor stage
Dilation stage initiated by regular painful contractions of the uterus
2nd labor stage
Expulsion stage that ends with delivery of the baby
3rd labor stage
Placental stage The placenta and fetal membranes (afterbirth) are expelled
4th labor stage
Recovery stage in which contractions of the uterus (oxytocin, prostaglandins) constrict the spiral arteries (no excessive bleeding)
What is dizygotic?
Most common twins (hereditary hyperovulation trait)
Blastocysts implanted separately; separate placentas; 2 chorions, 2 amnions
or
Blastocysts implanted close to each other (fused)
different genes
Monozygotic twins 2/3
From one zygote by division of the inner cell mass. After two cell stage it divdvides into two inner cell masses. only 1 placenta, 1 chorionic sac, two amniotic sacs. PLacental vessels can be either separated or united by anastomosis (unbalanced blood flow: TTTS twin to twin transfusion syndrome)
Monozygotic twins 1/3
From one zygote, two blastocysts; twi morulas develop. Separate chorionic sacs or fused, two amnions, separate placentas or fused
Monozygotic uncommon twins
50% fetal mortality. late division embryonic disc; fused embryos, can develop cojoined twins or parasitic twin
from what does organogenesis occur?
The primordia of all the organs and organ
systems appear from the 3 germ layers
What do Anterior visceral endoderm cells (AVE) promote?
hypoblast cells migrate to the future
cranial end of the embryo.= cranial / caudal axis
What establishes the caudal end?
Primitive streak initiated by Nodal (TGFß- family) The
node in the dorsal region is the organizer ( remember Hans Spemann and theory of induction in Xenopus embryos).
Nodal & HNF-3β maintain the node
What does the AVE transcribe?
Important for head formation: transcription
factors, OTX2, LIM1, HESX1, secreted factor cerberus. All are inhibitors of nodal (pro-caudal factor) activity in the cranial end of the embryo.
What does BMP-4 do?
Once the streak is formed, BMP-four (4) is secreted throughout the bilaminar disc (hatched areas). BMP- four (4) and fibroblast growth factor (FGF)- ventralize the mesoderm to contribute to kidneys, blood, and body wall mesoderm.
WHat do antagonists of BLM-4 do?
Goosecoid activates chordin, nogging and follistatin- inhibits BMP expression of the dorsal mesoderm in the cranial region. Contributes to regulation of head formation
Thus, ventralization is inhibited in the dorsal mesoderm of the cranial end of the embryo
What can happen if there is over expression of Goosecoid?
Gastrulation associated defects like cojoined twins
What does Brachyury (T) do?
gene-regulates dorsal mesoderm in middle and caudal regions. It encodes a transcription factor that binds to a T box in the DNA. It is expressed in the node, notochordal precursor cells and notochord.
Thus, ventralization is inhibited in the dorsal mesoderm of the middle and caudal regions of the embryo
What happens if there is less expression of brachyury?
sirenomelia
What transcription factors does the node and primitive streak express?
FGF8 which promotes nodal production that expresses 5-HT in left size promoting that nodal stays in left side. nodal in left side activates Lefty2 and PITX2 which maintain the left side. Having Shh in the notochord establishing the middle line and also having lefty1 in the left side, inhibits the nodal lfrom passing to the right side.
Which is the master gene of left side?
LEFTY2
What is Snail?
transcription factor associated
to the establishment of the right side
what are somites?
mesoderm at both sides of the notochord proliferates to form a thick longitudinal column of paraxial mesoderm
Where does fusion of the neural fold begin?
in the cervical region (5th somite) and proceeds cranially and caudally
What is the midgut, hindgut and foregut?
When the folds begin produces these regions, midgut is remnants of yolk sac.
caudal and cranial regions only have what layers?
Ectoderm and endoderm
What are the derivatives of ectoderm?
neuroectoderm (neural crest and neural tube)
surface ectoderm
What are the derivatives of mesoderm?
paraxial mesoderm, intermediate mesoderm, lateral mesoderm
What are the derivatives of endoderm?
Epithelial parts of respiratory organs, epithelium of gastro…thyroid etc
WHat derivative of surface ectoderm?
(epithelial layer of the skin)
and its derivatives: nails, hair, lens of
eyes, epithelium of sweat glands,
sebaceous glands, mammary glands
- Sensory placodes (auditory and nasal
placodes - Terminal portion of the anal canal, oral
cavity and its derivatives: parotid glands,
adenohypophysis (anterior part of
adenohypophysis) and enamel of teeth
What deos the neural tube form?
- Nervous tissue of the brain (including macroglia)
- Spinal cord
- Pineal gland
- Retina and optic nerve
- Posterior part of pituitary gland
Neural crest cells give origin to….
Peripheral nervous system (including ganglia
cells and Schwann cells)
* Chromaffin cells of the adrenal medulla
* Melanocytes
* Mesenchyme and visceral skeleton of head and
neck
* Dental papilla
* Parafollicular (C) cells of thyroid gland
* Meninges (leptomeninges ie. arachnoid and pia mater); dura
mater originates from mesoderm
What segments organized into the paraxial mesoderm?
somitomeres (mesodermal cells)
Where do somites appear?
First appears (~20th day) in the cephalic
(occipital) region, then cephalocaudally
* In the head region, somitomeres contribute
to mesenchyme of the head
What is scletotome?
tendon cartilage of bone component and vertebral column, ribs
What is myotome?
limb precursors and muscles of the back (epaxial musculature)
What is dermatome?
dermis and subcutaneous tissue of the skin in neck, back, sides
Intermediate mesoderm gives rise to?
irogenital system, gonads, ducts and accessory glands
somatopleure
Parietal (somatic) mesoderm + ectoderm
splanchnopleure
Visceral (splanchnic) mesoderm + endoderm
What are some derivatives of lateral plate mesoderm?
Primordial heart
* Blood and lymphatic cells
* Spleen
* Adrenal cortex (most medially located
lateral plate mesoderm also referred as intermediate mesoderm)
* Connective tissue and muscle of viscera
When does vasgulogenesis begin?
18 day (3rd week)
vasculogenesis-vesselsarise from blood islands
(mesoderm of yolk sac and lateral plate mesoderm)
-Angiogenesis-new vessels sprout from existing ones
What regulates the production of blood vessel formation?
VEGF
What are capillary hemangiomas
Abnormal vessels growth might be associated with high levels of IGF-1
From where do hematopoietic stem cell arise?
from mesoderm surrounding the aorta
(aorta-gonad-mesonephros region). Eventually, these cells will colonize the liver
(9 weeks) and spleen & thymus (12 weeks), which becomes the major
hematopoietic organs of the fetus.
Later (week 28), stem cells from the liver colonize the bone marrow (bloodforming
tissue
When does primordial cardiovascular system begim?End of 3rd week
End of 3rd week
How does the embryo look in the 5th week?
Cervical sinus is visible (landmark)
Mesonephric ridge
How does the embryo look in the 6th week?
Large hand plates Eyes are obvious
Digital rays Head larger than trunk
Spontaneous movements Auricular hillocks- external auditory canal and ear
Reflex responses to touch
How does the embryo look in the 7th week?
Notches between digital rays appear
Reduction of the communication between the yolk sac and the primordial gut (vitelline duct or omphaloenteric duct)
Umbilical herniation (physiological hernia)- intestines enter the extraembryonic coelom, because of fast growth of intestines and small abdominal cavity
How does the embryo look in the 8th week?
-Tail-like caudal eminence is present (stubby) at the beginning, but then disappears
-Band around the head- scalp vascular plexus
-Digits completely separated
-Purposeful limb movement- ossification occurs in the femur
-Distinct human characteristics, but still disproportion between head and trunk
-Sexless appearance
Estimation of Embryonic Age
Used internationally
Greatest length (GL)- 3rd and 4th weeks, embryos are straight
Crown-Rump-Length (CRL)- older than 4th weeks embryos, curved embryos
Crown-Heel-Length (CHL)- can be used beginning at 8th weeks (depends on
visible limbs during ultrasound).
Chorionic cavity (gestational sac) measurement is often used to determine
stage of pregnancy
