What are the 3 phases of fertilization?
Phase 1: Penetration of the corona radiata Phase 2: Sperm binding (SED1 protein) and penetration of the zona pellucida Phase 3: Fusion of sperm and oocyte cell membranes
What is the acrosome reaction?
Lysis by enzymes Fusion of the outer acrosomal membrane and sperm cell membrane, resulting in the release of acrosomal enzymes
Sequence of events in human fertilization
Acrosome intact (on sperm head) Acrosome vesiculates Sperm binds zona pellucida Sperm digests & moves through zona pellucida followed by sperm-egg biomembrane fusion Sperm nucleus enters egg cytoplasm
Fast component and Slow component in zona pellucida
What is the fast component?
Fast component: change in resting potential of oocyte plasma membrane prevents further binding of sperm
What is the slow component?
Slow component: release of cortical granules (lysosomes) containing enzymes that destroy sperm receptors (ZP3)
Penetrating the zona pellucida requires what?
Acrosomal enzymes, specifically acrosin
Zona Pellucida Proteins and Fertilization
1. Receptor for ZP3 on sperm head binds to ZP3 in egg zona pellucida 2. ZP3-Receptor binding leads to clustering of receptors to side of sperm head 3. Resulting acrosome reaction releases acrosin which digests hole through zona pellucida 4. ZP2 receptor binds to ZP2 keeping sperm attached to zona pellucida *Note: Experimental removal of carbohydrate residues from ZP3 prevents sperm-egg binding and fertilization
Where are the ZP3 receptors?
On the zona pellucida
What is required for the sperm to be able to fuse with the egg?
Immunoglobin superfamily protein Izumo A mutation in Izumo creates the inability for the sperm to fuse to the egg and undergo this acrosome reaction
Sperm head and tail enter oocyte Second meiotic division with production of second polar body Unequal contribution of cytoplasm, equal contribution of genetic material
(Fraternal/non-identical) Develop when two separate eggs are fertilized and implant in the uterus Result from the fertilization of 2 different eggs with 2 different sperms
(identical) Result from the fertilization of one egg and one sperm When a single fertilized egg splits into two genetically identical parts Share the same DNA set, but can actually look very different, but can also be identical twins
Polar (Half-identical) Twins
Polar body twins occur when the oocyte splits before fertilization and the polar body is also fertilized by a different sperm Twins share half their genes in common (from the mother) and the other half different (from the two sperm). They share some features of identical twins and some features of fraternal twins and are so-called half-identical twins DNA-based zygosity tests are currently not available to determine if twins are polar-body twins
Cells within one individual have different genetic makeup Some cells have normal number of chromosomes, others do not (one cell may have 46 chromosomes and another may be lacking one and only have 45)
Mitotic non-disjunction early in cellular division
Gonadal or tissue mosaicism
-Mosaic Down Syndrome -Segmental Neurofibromatosis (NF1) -McCune-Albright Syndrome: GNAS1 mutations
Mosaicism vs Chimerism
-Mosaic: genetically different cells, same zygote (e.g. Blaschko's lines) -Chimera: genetically different cells, different zygotes *Different color skin over body
-Multiple cell lines (genotypes) with different set of chromosomes in a single individual -Fraternal twins that "fuse" to form a single individual -Individual with bilateral "assymetry" penis/testicle and ovary/uterine tube; mix of Xy and XX (IVF) -40 cases of no genetic "relationship" between mother and offspring
X chromosome inactivation
-Early in embryogenesis in mammals, one X chromosome is functionally inactivated through a process called X chromosome inactivation (lyonization) -Because this inactivation occurs randomly, ALL NORMAL FEMALES HAVE ROUGHLY EQUAL POPULATIONS OF TWO GENETICALLY DIFFERENT CELL TYPES AND ARE THEREFORE A TYPE OF MOSAIC Cat: Paternal X=black Maternal X=orange -The tortoiseshell pattern of fine patches of black and orange reflects the pattern of X chromosome inactivation in the hair follicles
The process of nuclear fusion, whereby 2 haploid cells fuse into a single diploid cell or zygote takes about _____ hours
Fusion of pronuclei
Return to diploid chromosome number Mitotic division of the zygote begins Embryogenesis begins
A series of mitotic divisions of the zygote. It is asymmetrical (daughter cells are unequal in size) and asynchronous (only one cell will divide at a time) Oocyte + fertilization--> zygote-->2 cell blastula-->4 cell blastula-->morula-->blastocyst
Consists of cells called blastomeres Oocyte + fertilization--> zygote-->blastula-->morula-->blastocyst
What is a morula?
A cluster of blastomeres (16-32 blastomeres) Gets more and more compact
Make up a blastula/blastocyst Are totipotent up to the 8-cell stage (i.e. each blastomere can form a complete embryo by itself).
Refers to a stem cell that can differentiate into every cell within the organism, including extraembryonic tissues
Is a group of cells that is small enough to fit into Roosevelt's eye on the face of a US dime
Involves fluid secreted within the morula that forms the blastocyst cavity, thus forming the blastocyst 1. The inner cell mass of the blastocyst is called the embryoblast (becomes the embryo). The embryoblast cells are pluripotent (can turn into ectoderm, mesoderm and endoderm) 2. The outer cell mass of the blastocyst is called the trophoblast (becomes the fetal portion of the placenta) Zona pellucida begins to dissipate
The outer cell mass of the blastocyst is called the trophoblast (becomes the fetal portion of the placenta)
Hatching of Human Embryo
Cells of blastocyst secrete proteases Proteases digest proteins in zona pellucida Embroyo escapes through digested zona pellucida Hatched blastocyst
Ability to differentiate into other cell types As the zygote starts turning into the morula, it is totipotent during these stages (cells dividing...2-->4-->8 etc)
What is a single totipotent stem cell?
Blastomere Can grow into an entire organism and even produce extra embryonic tissues
Pluripotent stem cells:
Cannot grow into a whole organism but can differentiate into cells derived from any of the three germ layers... Morula=Totipotent Inner Mass Cells (inside Blastocyst)=Pluripotent So...the earlier on, the more things the cell can do
Types of Twinning
1. Cleavage of early embryo 2. Splitting of Inner Cell Mass (ICM) 3. Incomplete division of ICM
Incomplete division of monozygotic twins Due to secondary fusion of ICM or development of 2 primitive streaks
When the blastocyst implants close to the internal os (opening) of the cervix, so that later in development, the placenta bridges the opening (placenta previa) and causes severe, even life-threatening bleeding in the second part of pregnancy and during delivery
Implantation taking place outside the uterus resulting in an ____
Extrauterine pregnancy, or ectopic pregnancy. May occur at any place in the abdominal cavity, ovary or uterine tube 95% of ectopic pregnancies occur in the uterine tube
When the blastocyst develops in the ovary proper
Causes a primary ovarian pregnancy
When the trophoblast develops and forms placental membranes, although little or no embryonic tissue is present. What is this condition called?
Hydatidiform mole Moles secrete high levels of hCG and may produce benign or malignant (invasive mole, choriocarcinoma) tumors
The trophoblast differentiates into what?
Cytotrophoblast and syncytiotrophoblast
Where does implantation occur?
Functional layer of the endometrium during the progestational (secretory) phase
Where are stem cells derived from?
Inner cell mass (ICM) of the embryo
Adult stem cells
Adult tissues contain stem cells that may also prove valuable in treating disease. These cells are restricted in their ability to form different cell types and are thus multipotent, not pluripotent.
25% of pregnancies end in spontaneous abortion
Result of chromosomal abnormalities
What are integrins?
Adhesion molecules Developing embryo "sticks" to endometrial lining
Inner Cell Mass (ICM)
Differentiation of the embryoblast into what?
Epiblast (columnar cells) and hypoblast (cuboidal cells). Together they make the bilaminar embryonic disk
2nd opportunity for cellular differentiation 1. Trophoblast cells differentiate 2. Embryoblast cells differentiate
Within the epiblast, clefts develop and form the amniotic cavity
Picture of epiblast/hypoblast and cavities
What is the purpose of the amniotic cavity?
Prevents desiccation (drying out)
The amniotic membrane is specialized to secrete the amniotic fluid that bathes the embryo
(Closer to epiblast)
What does hCG do?
(Human chorionic gonadotrophin)
Signals the ovary to continue to secrete hormones to maintain the pregnancy
Schedule of ovulation
Ovulation- Day 14
Expected menses-Day 28
Extraembryonic (XE) Mesoderm
- New layer of cells
- Derived from epiblast (and yolk sac)
- Area around the outside of the yolk sac and amniotic cavity
- Found between inner lining of cytotrophoblast and yolk sac
- Gives mechanical and trophic support
- *XE coelom begins as splits in XE mesoderm
- Uteroplacental circulation begins
Outside the embryo
Chorion is made from what?
Consists of the extraembryonic mesoderm, cytotrophoblast, and syncytiotrophoblast
The chorion=forms fetal part of placenta and secretes hCG, and suppresses mother's immune system so it won't attack embryo
What is hCG?
Glycoprotein produced by the syncytiotrophoblast and stimulates the production of progesterone by the corpus luteum (progesterone is essential for the maintenance of pregnancy until week 8). Placenta then takes over progesterone production
Wall of the body cavity (skeletal muscle)
Visceral, "internal organs"
What is found within the chorionic cavity?
Amnion and amniotic cavity are found inside the chorion
Excessive growth of the amniotic cavity obliterates the chorionic cavity and fills the uterine cavity
The chorion is like the outer layer of the whole circle, and within are the yolk sac and amnion (both enclosed smaller circles), and these two are connected via the embryo
Chorionic villus sampling
A type of prenatal diagnostic test to detect chromosomal problems that can result in genetic diseases and birth defects
It involves taking a small sample of part of the placenta (the chorionic villi) where it is attached to the wall of the uterus
Establishes the three definitive germ layers of the embryo: ectoderm, intraembryonic mesoderm and endoderm), forming a trilaminar embryonic disk (from bilaminar disk). These three germ layers give rise to all the tissues and organs of the adult
Cells at the primitive streak
Cells differentiate at the primitive streak and migrate to form a middle mesodermal layer, as well as displace most of the hypoblast cells to form an endodermal layer. The ectoderm forms from the epiblast
- Narrow line of cells appears on surface of embryonic disk
- Primitive streak is future axis of embryo
- Marks beginning of gastrulation
- Organizes embryo along a craniocaudal axis
*The incomplete separation of 2 primitive streaks may be another mechanism in the formation of conjoined twins
Elongation of the primitive streak is formed from what cells?
From a proliferation of epiblast cells
Cells migrate to center of embryo
Streak elongates with cells added to caudal end
Sacrococcygeal Teratoma (SCT)
- Most common congenital germ cell tumor
- Female predominance
- Possibly arises from multipotent cells from anterior portion of primitive streak
- Remnant of the primitive streak, and these pluripotent cells proliferate and form tumors
In utero intervention for SCT:
- Tumor is exposed through a small hysterotomy
Germ Layer Defects
- Caudal Dysplasia/Caudal regression syndrome or sacral agenesis
- Caused by abnormal gastrulation; the migration of mesoderm is disturbed
- Minor abnormalities to complete underdevelopment or fusion of the lower limbs
- VATERL- vertebral abnormalities, anal atresia, tracheoesophageal fistula, renal defects and limb defects
Major Occurrences in Week 3
- Appearance of primitive streak
- Differentiation of the three primary germ layers
- Development of the notochord
- Development of the notochord
What are the functions of the notochord? (3)
- Structure: acts as a rigid axis around which the embryo develops
- Skeletal: foundation upon which the vertebral column (vertebral bodies) will form
- Induction: will bring about formation of the neural tube (future nervous system)
- Rare form of cancer that occurs in the bones of the skull and spine
- Most common in occipital region of sacrococcygeal region
- More common in middle age males
- Thought to arise from remnants of the notochord
- Treatment: surgical resection
- Prognosis: depends on size, location and extent of skeletal involvement
Serves as a scaffold for the formation of the spinal column
High doses of alcohol can kill cells in the anterior midline of the germ disk, producing a deficiency of the midline in craniofacial structures resulting in holoprosencephaly
Appearance: eyes are very close together (can look like there is one eye),
Caudal dysgenesis (sirenomelia)
Insufficient mesoderm is formed in the caudalmost region of the embryo
Fusion of lower limbs, vertebral abnormalities, anaomalies of the genital organs, associated with maternal diabetes
An uncommon condition in which the heart and other organs of the body are transposed through the sagittal plane to lie on the opposite (left or right) side from the usual
They may also have abnormal cilia (Kartagener's syndrome)
Patients do not have complete situs inversus but appear to be predominantly bilaterally left-sided or right-sided. Also likely to have heart defects
Neurotransmitter serotonin (5HT) is important for establishing laterality
What is in the ectoderm, mesoderm and endoderm?
Ectoderm: skin, nervous system (girlfriend)
Mesoderm: muscles, skeletal, urinary
Endoderm: GI, pulmonary