Unit 1.L1-Gametogenesis Fertilization Flashcards
What are the two periods of human development?
- Prenatal….Period 1
- Postnatal……Period 2
What is Period 1 of human development?
- Prenatal Growth (development in utero, before birth)
- Starts from fertilization of an oocyte→Birth is the prenatal period
Also called Intrauterine growth
What are the 2 periods of Prenatal Growth (period 1)?
1a. Embryonic
1b. Fetal
Explain the Embryonic Period (1a) including the stages and number of days
Prenatal Period
- 23 stages; Day 1-Day 56 (carnegie stages)
- Defined by morphological changes
- Stage 1: Fertilization: Day 1
- Stage 23: Embryonic period over: Day 56
What is the Fetal Period (1b)? When do we see the most visible organ structures?
Prenatal Period
- 9th week to birth: differentiaiton and growth of tissues and organs
- Most visible organ structures form b/w 3rd-8th weeks
By the time you are at day 56 (9th week) organ fate is already set, you are just tiny. Fetal period you are now growing
What is period 2 of human development? How many phases and what is occuring?
- Postnatal Growth: w/ 5 phases
- Extrauterine development
What is the 1st phase of POSTnatal growth (period 2) of human development? What is the duration and what occurs?
- Infancy: Neonate: up to 1 month or younger(neonatal period)
- Transition from intrauterine to extrauterine exsistence
- Many changes in cardiovascular and respiratory system during transition
Many changes occurs in 1st month and need to remove fluid from lung and heart needs to change circulation
What is the 2nd phase of POSTnatal growth (period 2) of human development? What is the duration and what occurs?
-
Childhood: period between infancy up to puberty (1 month to puberty)
1. Teeth: The primary (deciduous) teeth continue to appear –> replaced by the secondary (permanent) teeth.
2. Bones: Active ossification (formation of bones, length of the body).
- Ossification occurs all the way until 25
- Lungs grow unti 8
What is the 3rd phase of POSTnatal growth (period 2) of human development? What occurs?
Pre-pubertal growth: Rapid acceleration of weight (growth spurt)
What is the 4th phase of POSTnatal growth (period 2) of human development?
- Puberty: Functionally capable of procreation (reproduction)
- Female: 1st signs by 8-11
- Males: 1st begins at age 9-12
What is the 5th phase of POSTnatal growth (period 2) of human development?
- Adulthood: Attainment of full growth/maturity
- 18-21 years of age (early phase)
- 21-25 years of age: Complete ossification (mature adult)
In the lateral view of a 7-week embryo, a frontal coronal section can be seen. What is the rostral view?
90 degree cut to coronal section on face/nose
The vertebral column (spine) develops ____ in the embryo
dorsally
The lungs develop ____ to the esophagus
ventrally
The sternum develops ____.
Ventrally
List the steps of Gametogenesis (Meiosis I & Meiosis II)
Week 1
- Homologous chromatids pairs & align: Total 23 pairs (2n=46 chromatids)
- Synthesis phase (S-phase): Chromatid pairs duplicate (4 chromatids-4n=92)
- Meiosis I: TWO DIPLOID homologous chromosomes does allelic crossover
- Metaphase: The two pairs (4n) arrange at meiotic spindle (4n=92 chromatids)
- Anaphase: The diploid chromosomes with the new alleles seperate (4n=92 chromatids)
- Telophase: The chromosomes goes to poles and cytokines begins (4n=92 chromatids)
- New diploid cells for Gametogenesis: (2n=46 chromosomes w/ newly swapped alleles)
- Meoisis II: Each diploid cells give rise to 2 haploid cells. (4 haploid gametes are formed from each diploid gonadal precursor cell in spermatogenesis; in oogenesis only one gamate formed, rest become polar bodies and dies)
What can abnormal gametogenesis cause?
- Causes Nondisjuction in chromosomes→abnormal gametes (sperm/egg).
- After fertilization, the gametes w/ numeric chromosome abnormalities (3n) cause: Trisomy 21 or Down Syndrome
- Examples
1. Nullisomy: loss of both pairs of chromosomes (ex. Turner’s syndrome)
2. Disomy: 2 pairs of chromosomes from same parent, none from the other
3. Trisomy: numeric chromosome abnormalities (3n)
Explain the steps of Meiosis I & II in Spermatogenesis?
- Dominant Spermatogonia in the seminiferous tubules mature in sperm at puberty
- At puberty mitosis of Spermatogonia→primary spermatocytes (largest cell)
- In Meiosis I: Primary spermatocyte (46 x 2n; XY, n=92 chromatids)→Secondary spermatocyte (smaller cells; 23 x 2n; XY=46)
- In Meiosis II: Secondary spermatocytes→4 haploid spermatids (smallest cells)
- SpermIOgenesis: converts spermatids into four mature sperms (Haploid)
- Sertoli cells lining the seminiferous tubules support and nurture the sperm
- Mature Sperms→seminiferous tubules & are stored in the epididymis
- Spermatogonia takes 2 months to form mature sperm
What is Oogenesis?
PGCs (progenitor germ cells) make Oogonia→Mature Oocytes
Explain the steps of Meiosis I & II in Oogenesis?
- Oogenesis (Ovaries): Diploid Oogonium (PGCs)→grow/mature into primary oocytes (in follicles)
- The pimary oocyte start meoisis I but STOP at prophase I in Embryo
- At puberty : Primary oocytes completes Meoisis I→ 1 st polar body + Diploid (2n) Secondary oocyte
- At ovulation, secondary occyte undergoes Meiosis-II up metaphase and stalls
- Completion of Meiosis II occurs after sperm entry and the haploid secondary occyte (23 single chromatids, 1n) is called the Ootid (has male & female nucleus) before male & female chromosome mixing and deplodization/zygotization occcurs
What is the two stages of Oocyte Maturation?
- Prenatal/pre-puberty Maturation
- Postnatal/at puberty Maturation
Explain the Prenatal/pre-puberty Maturation of Oocyte maturation
- In the fetus, Oogonia proliferate by mitosis to form Primary Oocytes at birth.
- A single layered folliculae cells surround the Oocyte: Primordial Follicle
- The primary oocytes remain dormant in a Growing Follicle until puberty
- At puberty, the Primordial Follilcle→Ovarian Follicle
Explain the Postnatal/at puberty Maturation of Occyte maturation
- At Puberty the Primary Oocyte enlarges w/ follicular cells changing shape: Squamous→Cudoidal→Columnar cells→Ovarian Follicle
- Primary Oocyte is surrounded by Zona Pellucida (acellular glycoproteins)
- Meiosis-I:Primary Oocyte divides→Secondary Oocyte + First polar body & follicular fluid-filled space Antrum is formed
- Meosis II up to metaphase: At ovulation, secondary oocyte undergoes meiosis II & stalls at metphase
- Meiosis II is completed during fertilization, to form a Zygote + second polar body
- At puberty: One Ovarian follicle matures each month and Ovulation occurs
How long does Oogenesis continue for and when does it stop?
- Continues til menopause
- Stops when menstral cycle cease
How many primary oocyte do you have as a neonate compared to puberty?
2 Million primary oocyte; neonate→40,000 remains at puberty
On average how many secondary oocytes ovulate (if contraceptive are not used)?
- Only 400 (20-35 yrs of age)
Describe the structure of a mature human sperm
- The Head: Nucleus + cap-like acrosome (hydrolytic enzymes)
- The Tail: Middle piece, Principle piece and End piece
Describe the structure of a mature secondary oocyte (after Meiosis I)
Surronded by zona pellucida and corona radiata
Explain the Maturation of an Ovarian Follicle
- Primary Oocyte→Continues to grows & later differentiate
- Proliferation of follicular cells→Estrogen production
- Zona pellucida is formed around the oocyte
- Theca folliculi (2 layered): Inner & outer
- Inner (Vascular theca interna)
- Outer (Glandular theca externa)
- Follicle splits, giving a fluid space Antrum & becomes: →Secondary Oocyte→Mature Oocyte
- FSH (follicle stimulating hormone) in early ovarian development
- LSH (luetinizing hormone) in late ovarian development induces Ovulation
What is the function of the inner and outer layer of the Theca folliculi (derived from ovarian follicle)?
- Inner: Vascular theca interna
- Outer: Glandular theca externa
- Inner (Vacular theca interna): Nutrtion to the follicle→produce Estrogen
- Outer (Glandular theca externa): Intestitial gland of the ovary→produce Prostaglandins
Explain the steps that induce Ovulation
- Under FSH and LH, at mid menstrual cycle, a bulge or Stigma appears
- Secondary oocyte detaches from the follicle→mature oocyte
- High Blood Estrogen causes a spike in LH, inducing Ovulation.
- Ovulation: (i) Increase in Intrafollicular pressure & (ii) Contraction of theca externa smooth muscle mediated by prostaglandins, ruptures the Stigma→Oocyte is expelled
- Oocyte (covered with Zona pellucida & Corona radiata)ready to be fertilized.
- The finger like fimbriae of uterine tube sweep the oocyte into the infundibulum
Stigma can pentrate wall of ovaries
What causes Ovulation?
High Blood estrogen causes a spike in LH which induces ovulation
When ovulation occurs what mediates the increase of intrafollicular pressure and contraction of theca externa smooth muscle?
Prostaglandins
What happens after the LH surge and ovulation?
LH surge→empty follicle & theca follculi→Glandular Corpus Luteum
Corpus Luteum
- Secretes what?
- Prepares for what?
- Secretes: Progesterone and Estrogen
- Prepares: the Endomertrium for the implantation of the fertilized Oocyte
What happens to the Corpus Luteum after fertilization?
- Enlarges to form a corpus luteum of pregnancy and increases its hormone production which helps convert the Zygote into multicellular Blastocyst
What does the Blastocyte make and explain its function?
Makes hCG (Human Chronic Gonadotropin) hormone and prevents degeneration of corpus luteum, which maintains secretion of progesterone and estrogen in a positive feed-back loop
What are the 3 parts of the Early Embryonic Phase?
- Blastogenesis
- Implantation of the Embryo
- Ceasing of the Menstrual Cycle
Early Embryonic Phase
Explain Blastogenesis
Part 1/3
- Cleavage of the zygote and formation of a blastocyst
- The blastocyst prepares to implant in the endometrium
Early Embryonic Phase
Explain what helps the Implantation of the Embryo
Part 2/3
- HCG is secreted by the outer epithelial cells of the blastocyst-the trophoblast (Syncytiotrophoblast)
- HCG keeps the corpus luteum secreting estrogens and progesterone (setting a positive feed-back loop, preparing the endometrium for implantation)
Trophoblast (Syncytiotrophoblast)-layer that attachs to endometrium
Early Embryonic Phase
Explain the Ceasing of Menstrual Cycle
Part 3/3
Endometrium is now ready for the pregnancy phase
No ischemia or loss of endometrium lining
What are the steps of transportation of the oocyte?
- The expelled secondary oocyte floats in the follicular fluid.
- The fimbriated end of the uterine tube turns to the ovary
- The finger-like fimbriae moves back & forth over the ovary in a sweeping action.
- The fluid current is produced by the mucosal cell cilia of the of the fimbriae, which “sweep” the oocyte into the funnel-shaped infundibulum of the uterine tube.
- The fertilized oocyte then goes→ampulla of the uterine tube by peristalsis and reaches the uterine lumen in 3-4 days.
What are the two phases in sperm discharge?
- Emmision
- Ejaculation
What is emission?
- Peristalsis of the ductus deferens pushes the sperms to the prostatic part of the urethra through ejaculatory ducts
- Secretions d/t Symphathetic response from the: seminal glands (vesicle), prostate and bulbourethral glands, produce sperm filled Semen
What are the secretions of sperm due to?
D/t Sympathetic response from the: seminal glands (vesicle), prostate, & bulbourethral glands, produce sperm filled Semen (keeps sperm healthy)
How does ejaculation work (sequence of events)?
- Closer of the vesicle sphincters of the bladder
- Contraction of the urethral & penial erectile muscle
- Semen is expelled via uretheral orifice ~600 mill sperms are deposited at the external OS & fornix of the vagina during intercourse
How does the transport of the sperms to the oviduct happen?
Capacitation
- Changes in cell surface of the sperm
- Required for proper attachment and penetration of the zona pellucida when the sperm encounter the oocyte
How does the activation of sperms in the oviduct happen?
Capacitation, Acrosome Reaction and Penetration in the Oocyte
- Capacitation: Removal of Glycoproteins + Seminal Proteins from the Acrosome (initiating “Acrosome Reaction”
- Occurs in 7 hrs in the ovidult d/t uterine secretions
- Acrosomal perforations release hydrolytic enzymes when the sperm touchs the “Corona radiata”
- Acrosome binds glycoprotein (ZP3) on the zona pellucida & acrosome enzymes digests the zona pellucida
- Sperm nucleus (head) & tail enters the cytoplasm of the oocyte.
How does Fertilzation occur at a cellular level?
- Oocyte with 23 identical chromatid pairs (Meiosis-II-Metaphase)
- Sperm entry completes meiosis-II, forming the female haploid pronucleus (n=23 haploid) + 2nd polar body
- The sperm head becomes the male pronucleus (n=23 haploid).
(This cell with the male + female pronuclei is called the OOTID) - Fusion of Pronuclei→ Zygote with 23 diploid chromosomes
List the main points that summarizes phases of Fertilization
- Passage of a sperm through the corona radiata.
- Penetration of the zona pellucida.
- Fusion of cell membranes of the oocyte and sperm.
- Second meiotic division of the oocyte to form the pronucleus.
- Formation of the male pronucleus.
- Formation of the Ootid with male & female pronucleus.
- Chromosomal mixing & sex determination at fertilization by the kind of sperm (X or Y) that fertilizes the oocyte.
What happens with the cleavage of the zygote?
Week 1
Zygote: Cleavage stages: 30 hrs p.f. (post fertilization), Zygote divides→smaller blastomeres.
- A-D:Morula: 12-32 cell stage (3-4 days)
- E:Early blastocyst: The zona pellucida degrades (5 days).
- F: Late Blastocyst: Zona pellucida degenerates; blastocyst enlarges & blastomeres align, tighten & undergo cell-cell adhesion, causing “Compaction” during morula stage.
- F: Embryoblast: Compaction segregates cells into inner cell mass (ICM) or (1) embryoblast outer cells ((2) trophoblast layer) and a uterine fluid filled space; (3) Blastocystic cavity
Morula also 8-32 cell stage; after 8 cell stage changes occur in the cytoplasm
What is the state of the blastocystic cavity and zona pellucida at day 4 compared to day 4.5?
Week 1
!2 hrs difference
- Day 4: The blastocytic cavity is just beginning to form. The zona pellucida is undergoing degradation.
- Day 4.5: The blastocyst cavity has enlarged and the embryoblast and trophoblast are clearly defined. The zona pellucida has completely dissolved.
How does implatation of the embryo occur?
Week 1
- At Day 6: the trophoblast of the blastocyst attaches to the endometrial epithelium at the embryonic pole(the ICM side)
- By the end of Day 6: Finger-like processes of “Syncytiotrophoblast” produces enzymes that invade and ‘“dissolves” the endometrial epithelium and the connective tissue surrounding it
ICM: Inner cell mass
What occurs at the end of the first week (Day 7)?
- The Attached Trophblast proliferates rapidly and differentiaties into two layers
1. Cytotrophoblast (inner layer)
2. Syncytiotrophoblast (outer layer) consisting of a mutlinucleated protoplasmic mass w/ no cell boundaries -
Attached Blastocyst
1. The implanted blastocyst is nourished by the endometrium
2. The primary endoderm (Hypoblast; yellow cuboidal cell lining) appears on the bottom surface of the embryoblast facing the blastocystic cavity
Where is the primary endoderm located?
Hypoblast
- Appears on the bottom-surface of the embryoblast facing the blastocystic cavity
List the main points that summerize the first week of embryo development
- Oogenesis: Oocytes made in ovaries are expelled in the Oviduct.
- Fertilization: Fimbriae of the uterine tubes sweep the oocyte into the ampulla, where it is fertilized by a sperm.
- (Oocyte touches sperm to completes meiosis II, becoming a mature oocyte (haploid; 23, 1n) & the 2nd polar body.
- The sperm enter the oocyte forming OOTID
- M + F pronuclei fuse & chromosome mixing (46; 2n) → Zygote
- Day 3: Zygote divides into 8-32 Blastomeres→ “Morula” stage
- Day 5, after Cell Compaction, it becomes a Blastocyst (ICM): (1) Embryoblast (2) Trophoblast and (3) Blastocystic cavity
- Day 6: Zona pellucida dissolves & trophoblast attaches to the endometrial epithelium via finger-like projections of the syncytiotrophoblast
- Day 7: A cuboidal cell layer of hypoblast forms on the inner-deep surface of the embryoblast, giving rise to primary endodermal layer (hypoblast)
What is Mittelschmerz?
- Pain during Ovulation
- A variable of mild abdominal pain occurs during ovulation in some women
- Ovulation cause bleeding into the peritoneal cavity, leading to abrupt, constant pain in the lower abdomen.
- Mittelschmerz is a secondary indicator of ovulation; primary being elevation of basal body temperature
Occurs in girls around 15
What is Anovulation?
- Women may not ovulate (anovulation) due to lack of gonadotropins
- Ovulation can be induced by giving gonadotropins or an ovulatory agent such as CLOMIPHENE
- CLOMIPHENE stimulates the release of pituitary gonadotropins (FSH and LH), resulting in multiple ovulations with high chance of multiple pregnancies (7-8 embryos survive to birth)
- Clomiphene binds to estrogen receptors so estrogen does not bind and the body thinks it has low estrogen
What is Anovulatory Menstrual Cycles & Ovarian Hypofunction?
- Without ovulation, an anovulatory menstrual cycle occurs. (no egg)
- Proliferative endometrium is seen, but no luteal phase seen→as corpus luteum does not form. ⭐️
- Estrogen/estrogenic birth control pills acts on the hypothalamus/pituitary gland; inhibits secretion of FSH/ LH→no ovulation. ⭐️
What is the normal amount of sperm in semen?
100 million sperms/per mL of semen in normal males & is variable in normal males (range: 20-100 million).
Male Infertility (30-50% of involuntary childless couples)
What are five reasons of male infertility?
- Low sperm count (< 10 million sperms/mL of semen)
- Immotile and abmormal sperm
- > 50% of spern non-motile after 2 hrs
- Medications, drugs, endocrine disorders, pollutants, cigarette smoking
- Obstruction of a gential duct (blocked ductus deferens)
What is a vasectomy?
- Surgical removal or blocked ductus deferens (vas deferens); no sperms in the semen
- Reversal of vasectomy is surgically feasible
What is dispermy and tripoidy?
- Normally one sperm enters the oocyte and fertilizes it due to polymerization of glycoprotein in Zona Pellucida
- If TWO SPERMS fertilize an ovum (dispermy), a Triploid zygote (69 chromosomes) is formed, causing spontaneous abortions and death to fetus shortly after birth
What are the 3 periods of the “in Utero” Phase
- Initial Period: 1st week of development
- Embryonic Period: 2-8th week
- Fetal Period: 9th week→Birth
“in Utero”- from embryo to fetus
What is the Embryoblast doing on Day 7 (Week 1)?
Forming a disc like structure attached to the endometrium
Where does the implanted blastocyst starts getting nourishment?
Day 7 (Week 1)
From the endometrium
Where does the primary endoderm (Hypoblast) appear on Day 7 (week 1)?
On the bottom-surface of the embryoblast facing the blastocystic cavity
What happens the Embryoblast disc at the beginning of Week 2 (Day 8)?
- Becomes “bilaminar”
1. Epiblast
2. Hypoblast
What does the Embryo disc later form?
Wk 2, Day 8
3 germ layers & Progenitor Germ Cells (PGCs), i.e., all tissues of the body
Day 8: Implantation of the Blastocyst & the Bilaminar Embryo
The trophoblast contacts the endometrium and gives rise to what?
Wk 2, Day 8
5 The Extraembryonic Structures
1. Amnion
2. Amniotic cavity
3. Umbilical Vesicle (Blastocystic cavity)
4. Connecting stalk
5. Chrionic Sac
NOTE: 4&5 are not formed yet
What is another name for implantation?
How big is the embryo?
Wk 2, Day 8
Conceptus (0.1 mm)
Cannot see it
Explain the roof and floor of the embryoblast
Wk 2, Day 8
- Roof: Aminoblast that are cuboidal
- Floor: Columnar cells and this is where the embryo grows from
- The amniotic cavity is between the two
What are the 2 layers the Trophoblast differentiate into?
Wk 2, Day ~8
- Cytotrophoblast
- Syncytiotrophoblast
What is the Cytotrophoblast?
Wk 2, Day ~8
(Inner layer of trophoblast) Cells, which migrate out of the endoderm & surrounds the Exoceolomic cavity
What is the Exocoelomic cavity?
(Also blastocystic cavity), or umbilical vesicle or yolk sac
What is the Syncytiotrophoblast?
Day ~8
(outer layer of trophoblast) Cells invading & hydrolyzing the endometrium. This helps in implantation
What is the epithelial type of:
- Cytotrophoblast
- Hypoblast
- Exocelomic membrane
- Cytotrophoblast: Cuboidal
- Hypoblast: Cuboidal
- Exocelomic membrane: Squamous
Hyoblast differentiates into exocoelomic membrane (cuboidal to squamous)
Where is the blastocyst located by Day ~8?
Wk 2, Day ~8
Half inside the endometrium
What are important structures formed by day ~8 and how are they formed?
Wk 2, Day ~8
Amnion, Amniotic Cavity & Exocoelomic Membrane
- Amnion emerges from the top-most layer of the epiblast
- A slit-like amniotic cavity emerges below the Amnion
- Exocoelomic membrane is made of squamous hypoblast derivates
What structure emerges from the top layer of the epiblast?
Wk 2, Day ~8
Amnion
What emerges from below the Amnion (aminoblasts)?
Wk 2, Day ~8
A slit-like amniotic cavity
- Roof of amnion is made up of what?
- Amniotic cavity form what?
Wk 2, Day ~8
- Aminoblasts
- Entire Embryo
What is produced by the endometrium and what does it cause during day 9?
Wk 2, Day 9
- Produces Microvilli, integrins, cytokines, prostaglandins, hormones (hCG, progesterone), growth factors and proteinases that cause endometrial cell apoptosis and makes it receptive to attach to the blastocyst
- Known as Synchronization
If this does not occur (when estrogen: progesterone ratio is off), there will be a miscarriage
What does the Syncytiotrophoblast produce during day 9?
Wk 2, Day 9
Produces hCG, which enters the maternal blood via endometrial lacunae
What is the function of hCG produced by Syncytiotrophoblast?
Wk 2, Day 9
Enhances estrogen/progesterone production in the corpus luteum in the ovary during pregnancy
Why does the corpus luteum secrete estrogen/progesterone?
Wk 2, Day 9
To pepare and maintain the placenta for nourishment of the embryo
What is the basis for pregnancy test?
Wk 2, Day 9
hCG in maternal blood
Together blood islands and synctiotrophoblast form what?
Wk 2, Day 9
Lacunae, where pumping blood of mom into synctiotrophoblast
What is the endometrial epithelial defect?
Wk 2, Day 9
Damage to the endometrium and the blood will come out on the 9th or 10th day of pregnancy
On Day 10: Amniotic cavity appears above the ___________
Wk 2
Embryoblasts
On Day 10: What seperates from the epiblast and what does it form?
Wk 2
Aminoblasts seperate from the epiblast and form the Amnion, around the amniotic cavity
What is the Epiblast?
Wk 2, Day 10
Thick columnar cells facing the amniotic cavity
What is the Hypoblast?
Wk 2, Day 10
Small cuboidal cells facing the Exocoelomic cavity, which is now called the Primary Umbilical Vesicle (PUV)
Amnion roof has what type of cells and what do they do?
Wk 2, Day 10
Squamous cells and secrete fluid b/c the cells cannot be dry
Where does the Extraembryonic mesoderm come from?
Wk 2, Day 10
Transdifferentiation of the hypoblast (goes out) and trophoblast (goes in)
Where is the Primary Umbilical Vesicle (PUV) cells derived from?
WK 2, Day 10
Hypoblast + Cytotrophoblast which form the Extraembryonic mesoderm
What does the Extraembyronic mesoderm surround?
Wk 2, Day 10
The Amnion, Embryonic disc & Primary Umbilical Vesicle w/ Exocoelomic cavity/Yolk sac
What is the function of eroded glands and blood in the lacunar network?
Wk 2, Day 10
Provide nutrition to the embryo via Primordial “uteroplacental circulation”
What closes the Endometrial Epithelial Defect?
Wk 2, Day 10
Blood Coagulum (fibrin plug)
How is the “Intervillous spaces” of the placenta formed?
Wk 2, Day 12
By Uterine glands erode, Lacunar networks form and make the synctiotrophoblast sponge-like
- The endometrial capillaries form what?
- Under the influence of what?
- What do sinusoid form?
Wk 2, Day 12
- Maternal sinusoids under the influence of estrogen & progesterone.
- Sinusoids form blood vessels in the endometrial stroma
The Extraembryonic mesoderm splits to form what?
Wk 2, Day 12
- Extraembryonic Coelomic space→the future Chronic cavity
Hypoblast cells contribute to what?
Wk 2, Day 12
Extra-embryonic endodermal lining (exocoelomic membrane) of the primary umbilicial vesicle (yolk sac)
Endometrial epithelial defect persists at Day12 & remains plugged by?
Wk 2, Day 12
Fibrin plug
When does the endometrial epithelial defect disappears and contagious endometrial epithelial layer is seen?
Day 13 (Week 2)
What does the primary umbilical vesicle do? and what surrounds it?
Wk 2, Day 13
Extends downwards & is surrounded by the extraembryonic coelom
What structure appears at Day 13 and will fuse with sinuosids?
Wk 2, Day 13
Primary Chrionic Villi
How does the extraembryonic coelom splits the extraembryonic mesoderm?
Wk 2, Day 13
- Extraembryonic Somatic Mesoderm (top): lines the amnion & the embryo body (soma) & trophoblast
- Extraembryonic Splanchnic Mesoderm(bottom): surrounds the umblicial vesicle
What happens to the primary umbilical vesicle (PUV)?
Wk 2. Day 14
- “Pinching off” to form the Secondary umbilical yolk sac, leaving a remnant of the primary yolk sac
Where does the Primary Chorionic Villi protrudes at?
Wk 2, Day 14
The connecting stalk of the outermost fetal layer, the “Chorion”
What is the Chorion and how is it made?
Wk 2, Day 14
- The outermost fetal layer
- Made of extraembryonic somatic mesoderm (top) and the two layers of the cytotrophoblast
What does the Chorion form?
Wk 2, Day 14
A sac called the Chrionic Sac with the chorionic cavity
At Day 14: The embryo “hangs” in the _________ and is only attached by the ___________ for nourishment from the __________ and later ___________
Wk 2, Day 14
The embryo “hangs” in the chorionic cavity and is only attached by the connecting stalk for nourishment from the chorionic villi & later placenta.
At Day 14: What does the Hypoblast cells form and how?
Wk 2, Day 14
Hypoblastic cells (in a localized area) become columnar and form a thicken circular area, the prechordal plate
What does the prechordal plate do?
Wk 2, Day 14
- Demarcating (determining) the future mouth and head region
- Embryonic Cranial-Caudal directionality is established
At day 14 what structure is large? And which structures are visible?
Wk 2, Day 14
- The Extraembryonic coelom is large
- The connecting stalk, amnion, chorion & chorionic villi and future chorinic cavity are visible
What does the Epiblast eventually become?
- Ectoderm of amnion
- Embryonic ectoderm (1 of 3 germ layers)
- Primative streak (origin of the 2 other germ layers)
Summary of Implantation I from Days 5-10
- Day 5:the zona pellucida (zp) degenerates post fertilization (pf).
- Day 6: Loss of zona pellucida allows the blastocyst to grow & adhere to the endometrial epithelium
- Day 7: Initiation of blastocyst attachment begins: Trophoblast differentiates into syncytiotrophoblast and the cytotrophoblast.
- Day 8: The syncytiotrophoblast secrets hydrolytic enzymes and erodes endometrial tissues.
- Day 8: Hypoblast & Epiblast are well defined after the embryoblast splits
- Day 8-9: Amnion and Amniotic cavity is well-defined; roof of the embryoblast forms the Amnioblast (Amnion)
- Day 9: the blastocyst begins to embed in the endometrium.
- Day 10: blood-filled lacunae appear in the syncytiotrophoblast
Summary of Implantation II from Day 10 to Day 14
- Day 10-11: the blastocyst is buried in the endometrial epithelium closing the plug
- Day 11: Lacunar networks form
by fusion of adjacent lacunae. - Day 11-12: the syncytiotrophoblast erodes endometrial blood vessels, allowing maternal blood to diffuse in and out of lacunar networks, which initiates the uteroplacental circulation.
- Day 12-13: the endometrial epithelium defect is repaired & contiguous epithelium is formed.
- Day 13-14: Primary chorionic villi, Chorion & its Sac develop
- Day 14: Thick columnar Hypobastic cells develop into prechordal plate
- Day 14: Connecting stalk, Chorion, Chorionic Villi & Future Chorionic cavity formed.
Summary of Embryonic Second Week
- Rapid proliferation and differentiation of the trophoblastduring blastocyst implantation in the uterine endometrium.
- Decidual reaction dissolves the endometrial tissues and makes it receptive to implantation of the blastocyst.
- Theembryoblast differentiates into abilaminar embryonic disc (upper layer-epiblast &lower layer-hypoblast).
- The primary umbilical vesicle formsandextraembryonic mesoderm develops.
- The amniotic cavityappearsbetween the cytotrophoblast and embryoblast.
- Cavities form & fuse in the extraembryonic mesoderm, forming the extraembryonic coelom (cavity).
- Thesecondary umbilical vesicle develops by pinching of the primary umbilical vesicle (degenerates!)
- The Extraembryonic coelom becomes thechorionic cavity in the surrounding layer, the chorionic sac.
- Thickening of the hypoblast (Cuboidal→Columnar cells) forms thePrechordal plate, a precursor to the head & mouth,
defining the Cranio-Caudal directionality of the embryo.
What is Extrauterine Implantations?
- Blastocyst implanted outside the uterus (ectopic sites); a clinical condition called “Ectopic Pregnancy”
- Ampulla is the most common
- Ovary has the least common implantation
Where does Tubal Pregnancies moslty occur?
~95%-98% of ectopic implantation
- In the Uterine tubes (mostly ampulla & isthmus)
Increase in Ectopic pregnancy (1 in 80)=2% of all pregnancies
What is the main cause of maternal deaths (1st trimester)?
Tubal pregnancy
How do you diagnosis Ectopic pregnancies?
Endovaginal axial sonogram
What is Abdominal pregnancy?
Rare cases of Extrauterine Implantations
- Expulsion of the embryo from the fimbriated end into the abdominal cavity, leads to Rectouterine pouch implantation (abdominal).
- It may continue to full term and the fetus is delivered alive by laparotomy
What is Lithopedion?
Rare cases of Extrauterine Implantations
If an abdominal conceptus dies and is not detected; the fetus becomes calcified, forming a “stone fetus,” orlithopedion.
Explain Heterotopic pregnancies and Placenta Previa
Rare cases of Extrauterine Implantations
- Heterotrophic pregnancies: Simultaneous intrauterine and extrauterine pregnancies (1:8000). With “super-ovulation drugs” the chance of heterotopic pregnancies increase by 25 fold! (~3:1000).
- Placenta Previa: Implantation at the Internal Orifice (OS). Painless bleeding during the third trimester as the placenta partially or totally covers the opening of the mother’s cervix.
What are the signs, symptoms & diagnosis of Extrauterine Implantations?
- Abdominal pain & tenderness due to distention of the uterine tube.
- Abnormal vaginal bleeding & pain in the pelvic peritoneum (peritonitis).
- Ectopic pregnancies have low secretion rate of β-human chorionic gonadotropin (β-hCG),
giving false-negative pregnancy blood test (dangerous!). - Transvaginal ultrasonography can detect early ectopic tubal pregnancies
What are complications of Extrauterine Implantations?
Rupture of the Uterine Tube
- Hemorrhage into the peritoneal cavity & death of the embryo by week 8.
- Tubal rupture and hemorrhage causes maternal mortality
What are treatments of Extrauterine Implantations?
- Prompt diagnosis, aggressive intervention & surgical removal of the tube and conceptus.
- Extrauterine pregnancies in the abdomen is removed by laparotomy.
- Rare Cervical implantations needs removal of the uterus (hysterectomy)
What is the definition of Abortion?
- “A premature stoppage of development and expulsion of aconceptus or embryo or fetus from the uterus before it is viable & capable of living outside the uterus”.
- An “abortus” is any product (or all products) of an abortion
Abortionis derived from latin “aboriri”, means to miscarry.
What are the different types of Abortion?
- Threatened abortion
- Spontaneous abortion (miscarriage)
- Habitual abortion
- Induced abortion
- Complete abortion
- Missed abortion
Explain Threatened abortion
- Profuse vaginal bleeding with high possibility of abortion
- 25% of all clinically apparent pregnancies have this symptom and half of these (~12-13%) embryos ultimately abort, despite utmost clinical care.
Explain Spontaneous abortion (miscarriage)
Definition: “Pregnancy loss that occurs naturally before the 20th week of gestation”
- Highest Frequency: 3rd week of fertilization.
- ~15% of diagnosed pregnancies end in spontaneous abortion (first 12 weeks).
- > 50% of all known spontaneous abortions result from chromosomal abnormalities→Older women have high probability of nondisjunction during oogenesis→ abortion
Explain Habitual abortion
≥ 3 consecutive pregnancies result in spontaneous expulsion
of a dead or nonviable embryo or fetus
Explain Induced abortion
A medically induced birth before 20 weeks when the fetus is NOT viable ex vivo.
Explain Complete abortion
It is a process in which all products of conception (embryo and its membranes) are expelled from the uterus
Explain Missed abortion
It is the retention of a conceptus in the uterus after death of the embryo or fetus
What are ways to inhibit the implantation
- Morning-after pills
- Intrauterine devices (IUDs)
Explain the morning-after pills
- Large doses of progestins/estrogens for several days, right after unprotected sexual intercourse, usually may not prevent fertilization but often prevents implantation of the blastocyst.
- Examples:
1. High dose of Diethylstilbestrol (DES): Taken twice daily for 5- 6 days, accelerates passage of the cleaving zygote along the uterine tube. Mechanism: Huge amounts of estrogen alters estrogen:progesterone ratio & disrupts the endometrial preparation for implantation. (DO NOT USE-cancerious agents)
2. Plan B Drug (1999): Progestin-only (Levonorgestrel), Emergency Contraceptive Pill (ECP) taken within 72 hrs. after unprotected sex will prevent unwanted pregnancy (89% of times); but will not work in over-weight women >164 lbs). Mechanism: It stops release/movement of egg & prevent a sperm from fertilizing; thickens the vaginal fluid & alters the uterine wall.
Explain Intrauterine devices (IUDs)
- Interferes with implantation by causing a local inflammatory reaction
- Examples:
1. IUDs (Slow-release Progesterone): Disrupts the endometrial preparation for implantation.
2. IUDs with Copper Wire: - Copper is directly toxic to sperms
- Copper induces uterine endothelial secretions that is toxic to sperms.
- Copper induces local inflammation, rendering endometrial wall incompetent for implantation
