Midterm 1 Lectures 1-8 Flashcards
How is embryology research done?
- Model Organisms
- Stem Cells
- Organoids
Embryonic stem cells are removed from ______ stage embryo and are ________
Embryonic stem cells are removed from blastocyst stage embryo and are pluripotent
What are two groups of stem cells?
- Embryonic stem cells
- removed from blastocyst stage embryo
- Induced Pluripotent stem cells
- isolate adult somatic cells
- Revert back to stem cell stage with factors:
- Oct4
- Sox2
- Klf4
- c-Myc
Label the male reproductive system
Label the testis
Sperm develop while surrounded by _______ cells within the ___________
Sperm develop while surrounded by sertoli cells within the seminiferous tubules
Label the diagram of Spermatogenesis
Spermatogenesis takes ~ _________. Sperm then mature in the ________ for _______ months
As a final step, sperm undergo _______ in the female Reproductive tract
Spermatogenesis takes ~ 2 months. Sperm then mature in the epididymis for 2-3 months
As a final step, sperm undergo capacitation in the female Reproductive tract
Label the coronal section of the female reproductive tract
Ovaries contain many ________ follicles; a handful of which begin to develop each menstrual cycle
Ovaries contain many primordial follicles; a handful of which begin to develop each menstrual cycle
What makes up the primordial follicle?
The primary oocyte and a single layer of follicle cells
Primary oocyte is arrested in which stage?
Prophase I of meiosis (2N, 4C)
One of the first steps in follicular development is the formation of a tough glycoprotein layer between the oocyte and follicle cells called the __________
One of the first steps in follicular development is the formation of a tough glycoprotein layer between the oocyte and follicle cells called the zona pellucida
What produces the zona pellucida?
Secretions from both the oocyte and the follicle cells
As the follicle cells produce fluid they form the _______ within the follicle
As the follicle cells produce fluid they form the antrum within the follicle
When does the oocyte complete meiosis I? What is extruded after this completion?
Once the follicle is mature and in response to the LH surge the oocyte completes meiosis I (1N, 2C) and extrudes the first polar body
After meiosis I is complete, the oocyte starts ______ but is arrested in ______ until fertilization
After meiosis I is complete, the oocyte starts meiosis II but is arrested in metaphase II until fertilization
When does ovulation occur?
Day 14; dependent on LH surge (rapid rise in estrogen) When the follicle ruptures, releasing the oocyte with its loose covering of follicle cells. It is quickly swept into the fallopian tube by the actions of the fimbriae at the end of the tube
After ovulation and the release of the oocyte, what happens to the remainder of the follicle?
It collapses into folds and becomes the corpus luteum which secretes estrogen, progesterone and inhibin
How is the the capsule of the mature (graafian) follicle form?
Follicle cells (aka granulosa cells) recruit surrounding connective tissue cells to form a capsule (theca cells)
Label the theca cells, cumulus oophorus, corona radiata and granulosa cells
Describe the major hormones at play at the following stages and what they elicit:
- Menstrual phase
- Proliferative phase
- Ovulation
- Secretory Phase
Describe the major hormones at play at the following stages and what they elicit:
- Menstrual phase
- Low progesterone levels induce shedding of the stratum functionalis
- Proliferative phase
- Increasing estrogen levels cause the functionalis layer to re-develop.
- Glands are straight or moderately coiled
- Ovulation
- LH surge ; rapid rise in estrogen
- Secretory Phase
- Progesterone levels maintain functionalis and cause glands to become highly coiled and secretory
Menstrual Cycle:
Developing follicles secrete _____ which drives regrowth of the _______
Developing follicles secrete estrogen which drives regrowth of the endometrium
Menstrual cycle
After ovulation, corpus luteum secretes _______ which promotes maturation of the ________ such as:
Menstrual cycle
After ovulation, corpus luteum secretes progesterone which promotes maturation of the endometrium such as: increased vascularization and development of glands
Menstrual cycle:
In the absence of pregnancy, the ________ stops secreting progesterone after about 14 days. Effect on endometrium?
Menstrual cycle:
In the absence of pregnancy, the Corpus Luteum stops secreting progesterone after about 14 days
Blood vessels constrict in endometrium leading to ischemia and shedding
In response to GnRH the pituitary gland secretes:
LH and FSH
What is the effect of FSH in the ovary?
FSH promotes development of follicles (including estrogen secretion) by follicle cells
Acts on theca cells to convert androgens to estrogen
What are the 3 functions of LH?
- stimulates resumption of meiosis (completion of meiosis I : primary oocyte → secondary oocyte)
- Stimulates ovulation
- Promotes progesterone production by corpus luteum
LH acts on theca cells to synthesize androgens which then diffuse into granulosa cells where FSH promotes conversion from androgens to estrogen
IMAGE SLIDE 27
Describe hormone cycle throughout the menstrual cycle (FSH, estrogen, LH, Progesterone)
FSH and estrogen are elevated during the first half of the menstrual cycle
LH spikes just prior to ovulation in response to high estrogen
Progesterone is elevated in second half of the menstrual cycle
What are three challenges sperm face within the female reproductive tract
- acidic vagina
- immune cells in vagina and uterus
- travel through cervical mucus (more watery ovulation)
Granulosa cells are connected to the oocyte surface through _________
Granulosa cells are connected to the oocyte surface through granulosa cell processes which allow for cell-cell communication
Granulosa cells are surrounded by ___________
Granulosa cells are surrounded by extracellular matrix (mostly hyaluronic acid)
Sperm penetrates corona through ________
Sperm penetrates corona through mechanical action of the flagellum and action of enzymes on surface of acrosome
Sperm have receptors (________) that bind to _________ which results in breakdown of acrosomal membrane (acrosomal reaction)
Sperm have receptors (SPAM1 (sperm adhesion molecule 1 - hyaluronidase on sperm head) that bind to a zona pellucida glycoprotein which results in breakdown of acrosomal membrane (acrosomal reaction)
Once receptors from the sperm bind to ligands on the zona pellucida glycoprotein, the acrosome releases ________ which digest through the zona pellucida and allows sperm to enter the _______
Once receptors from the sperm bind to ligands on the zona pellucida glycoprotein, the acrosome releases hydrolytic enzymes (hyaluronidases)
Enzymes digest path through ZP and sperm enters the perivitelline space
what happens after sperm enters the Perivetelline space?
sperm plasma membrane fuses with egg plasma membrane and becomes incorporated into egg PM
Contents of sperm enter cytoplasm of oocyte
Oocyte resumes meiosis and extrudes another polar body
A Mature ovum (ootid) only exists once fertilized
Zona Pellucida is composed of glycoproteins _________
These act as specific ligands and bind to receptors on the head of the sperm triggering the ________ (species specificity)
The acrosome bursts and releases _______ that degrade the Zona pellucida
Zona Pellucida is composed of glycoproteins ZP1-4
These act as specific ligands and bind to receptors on the head of the sperm triggering the acrosomal reaction (species specificity)
The acrosome bursts and releases enzymes that degrade the Zona pellucida
How does the zygote prevent polyspermy?
After fertilization zygote develops a ZP block and a plasma membrane block to sperm entry
- Increase in intracellular Ca++ concentration triggers changes in ZP and PM
- Triggers release of cortical granules into perivitelline space
- Juno (egg ligand) is released from cell surface after fertilization
Chromosomal abnormalities most commonly arise because of _________ during ________
Chromosomal abnormalities most commonly arise because of nondisjunction during gametogenesis
What is monosomy?
Only one copy of chromosome
Autosomal monosomies usually not viable
XO can survive
What is trisomy?
Three copies of chromosome
Doesn’t have to be complete (ie can be only a portion of the extra chromosome (translocation) or only some cells have 3 copies (mosaicism)
What is trisomy 21?
- cause of down syndrome
- Typically, two copies of chromosome 21 fail to separate during meiosis
- Normal gamete fuses with one containing non-disjoined chromosomes 21
When does the zygote have one nucleus?
At no point do we have a zygote w/ one nucleus
Maternal and Paternal nuclei swell - Pronuclei Replicating their dna
What happens during the cleavage stage?
Rapid cell division (blastomeres) wherein cells become smaller and smaller but embryo remains same size
What is the difference between Epithelial and Mesenchymal Cells?
Epithelial cells:
- Stable adhesions
- Polarized (apical/basal)
- Arranged in layers
- Basal lamina (layer of ECM - reinforcing/stabilizing layer)
Mesenchymal cells:
- transient adhesions
- mobile
- unpolarized
- no basal lamina
What is the first cell differentiation even in the new embryo?
At ~16 cell stage
Compaction occurs
External cells and internal cells adopt different fates
What makes up the blastocyst?
Blastocyst is made of a thin outer layer of cells - trophoblast which gives rise to embryonic part of placenta and the inner cell mass/embryoblast that becomes the embryo and a blastocystic cavity (blastocoel)
What is the trophoblast?
Thin outer layer of cells that gives rise to embryonic part of the placenta
Tropho = to feed
What is the embryoblast (inner cell mass)?
Portion of the blastocytes that gives rise to embryo
What makes up the blastocyst?
Blastocyst is made of a thin outer layer of cells - trophoblast which gives rise to embryonic part of placenta and the inner cell mass/embryoblast that becomes the embryo
Define:
Totipotent
Pluripotent
Multipotent
Define:
- Totipotent
- cells that can give rise to any embryonic or extra-embryonic tissue (placenta/membrane) – blastomeres prior to differentiation
- Pluripotent
- Cells that give rise to any body tissue
- Multipotent
- Cells that can give rise to multiple tissue types
What is Hatching of the blastocyst? Why is it important
Hatching is the loss of the zona pellucida
- Hatching allows for growth of the embryo and attachment to the endometrial epithelium — allows implantation
When does implantation occur?
~ 6 days after fertilization
Blastocyst attaches to endometrial epithelium with embryoblast facing the the epithelium
Summary of First week:
Mature follicle → ruptures and releases oocyte → oocyte enters infundibulum of fallopian tube due to sweeping of fimbrae → cilia sweep oocyte to ampulla - fertilization typically occurs in distal ampulla) → Zygote travels through fallopian tube undergoing cleavage (2-cell stage - 4 cell stage - 8 cell stage - Morula (8-16cell)) → Enters uterus as early blastocyst → late blastocyst implants in uterine endometrium ~ day 6
What is a hydatidiform mole?
If sperm fertilizes an oocyte that has lost its nucleus, the cell can grow into a grape like mass called the hydatidiform mole
How is the endometrium prepped for implantation? (what stage is the endometrium in?)
- Endometrium is in the secretory phase of development at the same time the embryo is traveling down the fallopian tube and during implantation
- Corpus luteum secreting progesterone which maintain the stratum functionalis and cause glands to become highly coiled and secretory
- Surface of epithelium changes to promote attachment of embryo
- Vascular supply increases
- Glands form - expand and fill with secretions to nourish embryo
- Immune cells invade - develop tolerance to embryo
- Stromal cells undergo the decidual reaction
Describe what is happening in endometrial development during early/late proliferative phase and the secretory phase
- In proliferative phase, new cells and glands are made
- glands develop a coiled shape
- In secretory phase, glands expand and secrete abundantly - develop sawtooth appearance
- The spiral arteries become more and more tortuous - providing rich blood supply
What is decidualization (decidual reaction)?
- Occurs in response to progesterone from corpus luteum & signals from implanting embryo
- endometrial stromal cells (mesenchymal cells under epithelium) change gene expression, accumulate glycogen and lipids - become highly secretory)
- Stromal cells are now called decidual cells and the stroma is called the decidua (where embryo ends up after implantation)
- Secretions from decidual cells have multiple roles
- nourish
- promote implantation - limit extent
- regulate immune response
The ______ is the mothers tissue surrounding the embryo/fetus
The decidua is the mothers tissue surrounding the embryo/fetus
How does epithelium change during decidual reaction?
- Apical surfaces of endometrial epithelial cells - pinopodes
- only present transiently during receptive period
- may have a role in blastocyst adhesion
- Epithelial cells secrete factors and express surface proteins that promote attachment and invasion of the embryo
In IVF, the hormone _______ is used in place of LH
In IVF, the hormone hCG is used in place of LH
Difference between IVF and ICSI?
IVF spermatozoa and oocyte placed together in petri dish
ICSI spermatozoa injected directly into oocyte - important if theres a problem with sperm motility
Label:
Endometrial gland
Endometrial capillary
Endometrial epithelium
Trophoblast
Embryonic pole
Blastocyst
Abembryonic pole
Embryoblast
Approx day 7 - what happens to trophoblast cells contacting the endometrium?
Trophoblast cells contacting the endometrium begin to divide. some separate from blastocyst - fuse together and form a new layer
- Cytotrophoblast - inner layer
- Syncytiotrophoblast - outer layer, a syncytium of fused cells with no cell boundaries
Approx day 8
Happens to Syncytiotrophoblast?
Cytotrophoblast?
- Syncytiotrophoblast gradually increases in volume and invades underlying endometrium (secreting enzymes to breakdown endometrial tissue)
- villus processes actively migrate into tissue
- Cells detach from proliferating cytotrophoblast and fuse with the syncytium
What are the lacunae?
Cavities that develop in the syncytiotrophoblast approx day 9 - breakdown and phagocytose cells of decidua for nourishment by embryo
What is the coagulation plug?
At ~day 9 the endometrial epithelium nearly covers the embryo
Day 9 cont
- Maternal capillaries enlarge to form ________ - anastamose with the ________
- Synctiotrophoblasts produce _____ which enters maternal blood via the ____ and maintains the _______ (pregnancy test hormone)
Day 9 cont
- Maternal capillaries enlarge to form sinusoids - anastamose with the trophoblastic lacunae - blood flows from maternal sinusoids into lacunae to supply metabolic needs of developing embryo
- Synctiotrophoblasts produce hCG which enters maternal blood via the lacunae and maintains the corpus luteum (pregnancy test hormone)
Day 12
The lacunae grow and anastomose to form:
Day 12
The lacunae grow and anastomose (fuse) to form: a network to supply the increasing metabolic needs of the growing embryo
- form pools of blood around the embryo
- Syncytiotrophoblast surrounds entire embyro
Embryo at Day 8
2nd differentiation event:
- The second differentiation event: Embryoblast differentiates into two layers (bilaminar disc)
- epiblast
- “on top”
- Columnar epithelial
- Hypoblast
- “under”
- Cuboidal epithelium
- “under”
- epiblast
- Amniotic cavity between cells of embryoblast and overlying cytotrophoblast
What makes up the bilaminar disc? what does it give rise to?
The epiblast and hypoblast
Gives rise to the embryo
*first evidence of an axis
Top → dorsal (surface epiblast) embryo
Bottom → ventral embryo
What gives rise to the fetal portion of the placenta?
Derivatives of trophoblast
How is the amnion formed?
Cells migrate from the epiblast and line the amniotic cavity = amnion
Embryo and Day 8 cont
How is the primary yolk sac (umbilical vesicle) formed?
Cells migrate from the hypoblast and line the blastocystic cavity/blastocoel (this cavity is now the primary yolk sac or umbilical vesicle)
What new tissue forms beneath the cytotrophoblast layer?
Extraembryonic mesoderm
Between cytotrophoblast and amnion/yolk sac
Originates mainly from cells of the hypoblast and yolk sac
By day 12, fluid-filled spaces begin to form within the extraembryonic mesoderm (CT layer) and split this CT layer to form the ________
By day 12, fluid-filled spaces begin to form within the extraembryonic mesoderm (CT layer) and split this CT layer to form the extraembryonic coelom/ Chorionic cavity
- Some extraembryonic mesoderm left surrounding the embryo = inner coat
- Not a complete split as a connecting stalk remains which holds embryo within the cavity
Embryo at day 12
Development of the extraembryonic coelom splits the mesoderm into two layers:
Outer layers lines the _______
inner layer covers the _______
Embryo at day 12
Development of the extraembryonic coelom splits the mesoderm into two layers:
Outer layers lines the cytotrophoblast
inner layer covers the surface of the yolk sac and amnion
Embryo at Day 13
Three multi-layered membranes can now be distinguished:
- CHORION
- composed of cytotrophoblast, syncytiotrophoblast and extraembryonic mesoderm
- Yolk sac (within chorionic cavity)
- Cells derived from hypoblast and extraembryonic mesoderm
- Amnion (within chorionic cavity)
- Cells derived from epiblast and extraembryonic mesoderm
Day 13
Bilaminar disc with dorsal ______ and ventral ______ suspended in the ______ by a connecting stalk of ________
Day 13
Bilaminar disc with dorsal amnion and ventral yolk sac suspended in the chorionic sac by a connecting stalk of extraembryonic mesoderm
How is the definitive yolk sac formed?
Hypoblast cells
Second wave → Divide and migrate laterally (over inside of the extraembryonic mesoderm) → displace original lining of primary yolk sac → definitive yolk sac
Between days 12 and 13
Once the definitive yolk sac is complete, what happens to the primary yolk sac?
Day 14
Primary yolk sac becomes displaced to the abembryonic pole and degenerates
Development of Utero-Placental Circulation:
- During first week of development, embryo exchanges nutrients and wastes by _______
- As embryo grows, more efficient mechanism required
- __________ is the system by which maternal and fetal blood come into close proximity in the placenta for the exchange of gasses and metabolites
- During first week of development, embryo exchanges nutrients and wastes by simple diffusion
- As embryo grows, more efficient mechanism required
- Utero-placental circulation is the system by which maternal and fetal blood come into close proximity in the placenta for the exchange of gasses and metabolites
What is the first step in the development of uteroplacental circulation?
Formation of lacunae (filled with maternal blood) in the syncytiotrophoblast