The review Flashcards
What is the site of origin of the primordial germ cells in the early mammalian embryo?
Endodermal yolk sac
Define morphogenesis
generation of form or assumption of shape
Define differentiation
complex changes involved in progressive specialization of structure can result in the formation of luxury molecules
Define ontogeny
all developmental processes from contraception to death
Define determination
process by which a cell or part of an embryo becomes restricted to a pathway
At what sub-stage of meiosis I does pairing of homologous chromosomes occur?
Prophase- zygotene
At what stage of meiosis I does crossing-over occur?
- Pachytene of prophase I cross over begins, maximum coiling and tetrad formation
- Diplotene of prophase I cross over continues
- Diakinesis of prophase I cross over is complete, terminalization, spindle apparatus in place, and Nuclear Mem. Is disrupted
Compare trisomy, monosomy, aneuploidy, and polyploidy and explain how they relate to human gametogenesis.
Monosomy = 1 or (haploid)
trisomy = 3
Aneuploidy = Abnormal number of chromosomes
poly = more than two sets of chromosomes
During oogenesis, when does the first meiotic arrest occur?
Diplotene Stage of meiosis
During oogenesis, when does the second meiotic arrest occur?
Metaphase II
Describe the oogonium in the ovary during the early fetal period with relation to meiotic stage and cellular make-up of the follicle.
Fetal period
- Diploid oogonium not surrounded by follicle cells
- No follicle
- 1 chromatid chromsome
Which hormone is required for rapid transport of the egg through the isthmus of the oviduct?
Progesterone
What is the maximum number of germ cells present in the early female embryo, and how do these numbers change throughout the lifetime of the individual?
- in humans 7 million germ cells are present at embryonic midterm
- At birth about 2 million remain
- Shortly after birth, there are about 400,000 primary oocytes
- 40,000 will survive to puberty
- After puberty, at the beginning of each menstrual cycle, some of these oocytes resume meiosis until second metaphase
- About 400 will become ovulated
What is the fate of most of the female germ cells?
cells will become Atretic
Describe the oocyte at the time of ovulation.
oocytes Arrested at metaphase 2 while some become atrietic
What is the role of LH in resumption of meiosis? How is this related to MPF?
- Prior to ovulation
- Haploid secondary oocyte with corona radiata and thecal cells +haplod polar body
- Granulosa cells develop Fsh Receptors And LH receptors
- Circulating Fsh stimulates Granulosa cells to produce estrogen
- 2 chromatids / chromosome
- Meiosis resumes and is arrested ad metaphase II
- Due to LH surge which shuts down gap junctions between granulosa cells and oocyte
- cAMP concentration is reduced, allowing activation MPF
- Haploid secondary oocyte with corona radiata and thecal cells +haplod polar body
Distinguish between theca interna and externa and their relationships to angiogenesis factor and to LH receptors and testosterone?
- Theca externa
- Produce angiogenesis factor
- Theca interna
- With LH receptors
- Secrete testosterone
What components of the Graafian follicle form the corpus luteum?
Residues from thecca and granulosa cells of the graafin follcole proliferate and form a large glandular structure called corpus luteum
What is the function of aromatase?
Converts testosterone into 17beta estradiol
What hormone stimulates formation of LH receptors on granulosa cells?
Estrogen
What is the principal energy source for ejaculated spermatozoa?
Fructose
With regard to the passage of sperm through the female reproductive tract, where do they encounter the lowest pH?
Upper vagina (lowest PH 4.3 to 7.2)
Cervix (6.2 )
List the types of cells involved in spermatogenesis and indicate whether they are haploid or diploid.
Primorral germ cells (diploid)
Spermatogonium (diploid)
- type A forms stem cells
- type B with retinoic acid leave to become sperm
Primary Spermatocyte (diploid)
Two secondary spermatocytes (haploid)
Four spermatids (haploid)
4 spermatoza (haploid)
Which of the cellular stages of spermatogenesis lie outside the blood-testis barrier?
Spermatogonia (2N)
- type A and B
Describe the functions of Sertoli cells and cells of Leydig.
Sertoli cells
- Form an immunological barrier between the forming sperm cells and the rest of the body and spermatogonia
- Physical support and maintenance
- Maintain and coordinate spermatogenesis
- Secrete estrogen, inhibin, and anti-Mullerian factor
- Phagocytize residual bodies of sperm cells
Leydig Cells
- Synthesize testosterone from cholesterol
What role do LH, FSH, estrogen, testosterone, and inhibin play in sperm cell production? (ANSWER NEEDS TO BE WORKED ON)
LH
- Binds to LH receptors in intersitial cells of Leydig and causes those cells to synthesize testosterone from cholesterol
FSH
- Binds to FSH receptors on Sertoli cells
- Converts testosterone to estrogen and also synthesize Leydig cell stimulatory factor
Estrogen
Testosterone
- Stimulates formation of a new blood testis barrier closer to basal lamina
Inhibin
- hat suppresses follicle-stimulating hormone (FSH)
What changes to sperm occur in the head of the epididymus?
Maturation
- change in glycoproteins in plasma membrane of the sperm head
Describe the relationship and functions of each of the following hormones to the menstrual cycle—both the ovarian aspect of the cycle and the uterine aspect of the cycle. 1. FSH 2. LH 3. Estradiol 4. Progesterone
Follicular Phase
- FSH influences development of Graafian follicle
- Granulosa cells secrete estradiol
Ovulation
- Rise in FSH and sharp rise in LH
- Outer part of Graafian follicle remains behind and is made up of thecal cells that secrete progesterone
Luteal Phase
- Secretion of estrogen and progesterone from residual thecal and granulosa cells
- Lutenization of granulosa cells
- Granulosa lutein cells secrete increasing amounts of progesterone plus some estrogen
-
If fertilization doesn’t occur
- Corpus luteum regress and levels of progesterone and estradiol decrease resulting beginning of the next menstrual phase
- Inhibin, released by granulosa cells, inhibits secretion of gonadotropins, especially FSH resulting regression of corpus lutem
Menstrual phase
- Vasocontriction is mediated by prostaglandins
- Inflammatory cells invade the area and continue the process of the endometrial breakdown
Proliferation
- increase in estrodial
Secretory
- estrogen decrease and endometrial growth stops
A surge in which hormone level occurs 24 hours prior to ovulation?
LH with a slight rise in FSH
Describe the fate of the Graafian follicle after ovulation both in the event of fertilization and in the event of the absence of fertilization.
If fertilization does not occurs
- THe corpus luteum regressions and levels of progesterone and estradiol decrease resulting in beginning of the next menstrual phase
- inhibin, released by granulosa cell, inhibits secretion of gonadotropins, especially FSH, resulting in regression of corpus luteum
- Replacement of granulosa lutein cells with collagenous scar tissue results in formation of corpus albicans
- Break down of corpus luteum in absence of fertilization dye to apoptosis and uterine luteolytic factor
If fertilization occur
- chorioic gonadotropin from future placental tissues maintain functional corpus luteum
- granulosa lutein cells are replaced by theca lutein cells
- corpus luteum remains function for several months into pregnancy
What is the role of inhibin in relation to the ovarian cycle?
inhibin, released by granulosa cell, inhibits secretion of gonadotropins, especially FSH, resulting in regression of corpus luteum
What is the most likely site of fertilization?
fallopian tube where fertilization by a sperm may occur
Compare fertilization and menstrual age with regard to establishing the age of the embryo.
Fertilization age: from the time of fertilization
Menstrual age: from the last menstrual period; two weeks later than fertilization
Describe capacitation and explain where it occurs.
Required for sperm to undergo acrosomal reaction
occurs inside the uterine tube in isthmus
requires binding of sperm to tubal epithelium
involves
- removal of cholesterol from sperm surface
- acts to inhibit premature capacitation
- removal of glycoproteins (from epididymis)
Followed by a period of hyperactivity
What is the major action of hyaluronidase?
It helps to breakdown the hyaluronic acid component of the intercellular matrix between the corona radiata cells
Define “zygote.”
a diploid cell resulting from the fusion of two haploid gametes; a fertilized ovum
With regard to fertilization, what are the characteristics of the fast block to polyspermy?
consists of rapid depolarization of egg plasmalemma
-70 to +10mV within 2-3 seconds
may last a little longer in mammals (several minutes )
Fast block temporarily prevents polyspermy and allows time for egg to establish the slow block
With regard to fertilization, what are the characteristics of the slow block to polyspermy?
Most characterized by release of polysaccharides from cortical granules located just under the plasmalemma of the egg
- polysaccharides enter perivitelline space (b/w plasmalemma and zona pellucida and become hydrated)
- Hydration produces a swelling that increases the width of the perivitelline space
What roles do ZP3 and phospholipase C zeta play in egg activation?
ZP3
- ZP3 is one of four glycoproteins that make up ZP
- Attachment to sperm is mediated by ZP3 protein
- ZP3 stimulates acrosomal reaction in mammals
- acts through G proteins in the sperm plasma membrane
Phospholipase C zeta
- causes the release of calcium ion within the egg cytoplasm
What ion initiates metabolic activation of the egg? What are the results of this activation?
introduction of phospholipase C zeta in sperm causes release on calcium
- Initiates blocks to polyspermy
- stimulates increase in egge respiration and metabolism via the sodium hydrogen ion exchange mechanism
- results in an increase in PH and an increase in oxidative metabolism
What is the relation of Oct-4 to early cleavage?
expressed in developing oocytes and zygote
required to permit cleavage to proceed to 2 cell stage
expressed in all morula cells
may play a role in maintenance of undifferentiated states
What gene(s) is/are involved in the initiation of cleavage and the first cleavage division?
Oct-4:
• Expressed in developing oocytes and zygote
• Required to permit cleavage to proceed to 2-cell stage
• Expressed in all morula cells
• May play a role in the maintenance of the undifferentiated state
Describe the general structure of the blastocyst, including the different components.
- Surrounded by the zona pellucida
- large, eccentrically placed blastocoel
- Consists of two types of cells
- Outer layer of cell = trophoblast
- forms extraembryonic structures including placenta
- Inner mass of cells = inner cell mass
- forms embryo proper plus some extraembryonic structures
- Outer layer of cell = trophoblast
- Because of eccentric placement of blastocoel and inner cell mass the blastocyst is polarized
- embryonic pole marks the pole of the blastocyst where inner cell mass is located
- Abembryonic pole marks the opposite pole
Describe the role of specific transcription factors in the subdivision of the inner cell mass into epiblast and hypoblast.
-Nanog become epiblast cells -Gata 6 become hypoblast cells which are induced by FGF-4
At what point in development does most transcription via the embryonic genome begin to occur?
In invertebrates and non-mammalian vertebrates:
• Early control of cleavage is through gene products transcribed from the
maternal genome and embryonic gene products often do not appear until
after blastulation.
In mammalian embryos:
• Maternal gene products are produced but generally are degraded by the 2-cell
stage of development.
• By the four cell stage, most transcription is via the embryonic genome.
Be familiar with the methylation cycle and know at what point during early development would methylation be lowest in both the maternal and paternal chromosomes?
Methylation is the addition of methyl groups to specific regions of DNA
molecules; it inactivates genes, including enhancers and promoters.
• Methylation cycle:
• DNA of mature eggs and sperm is highly methylated.
• Demethylation of maternal and paternal genomes occurs shortly after
fertilization until the early morula.
• Remethylation of inner cell mass occurs until late blastocyst state.
• Methylation levels fall after primordial germ cells enter genital ridges.
• Remethylation occurs later during gametogenesis and may lead to
maternal/paternal imprinting.
What is the most common condition associated with spontaneously aborted embryos?
Polyploidy or abnormal chromosome number
Describe the inside-out hypothesis and cell polarity model theories for the establishment of polarity.
Inside-out-hypothesis
fate of blastomere is determined by its position within the embryo not from intrinsic properties
Cell polarity model
- cleavage plane parallel to outer surface of embryo
- outer daughter cell -> trophoblast cell (polar)
- cells pick up a patch of outer cell membrane containing microvilli and ezrin (microfilament-stabilizing protein)
- outer daughter cell -> trophoblast cell (polar)
- Cleavage plane perpendicular to outer surface of embryo
- both daughter cells become trophoblasts
Describe the role of Nanog, Sox2, and Oct-4 in early differentiation.
Cdx-2:
• Essential for trophoblast cell differentiation
• AntagonisMc toward →
- Oct-4:
- Expressed in developing oocytes and zygote
- Required to permit cleavage to proceed to 2-cell stage
- Expressed in all morula cells
- May play a role in the maintenance of the undifferentiated state
- Refer to page 42
Nanog:
• Produced by inner cells in late morula stage stage
• Maintains integrity of inner cell mass along with Oct-4
• Without Nanog inner cells differentiate into endoderm.
• Without Oct-4 inner cells differentiate into trophoblast.
Sox2:
• First expressed in 8-cell stage
• Along with Oct-4 it helps to control regulation of genes involved in
differentiation.
Compare Prader-Willi and Angelman syndromes and relate to genomic imprinting.
Prader-Willi
• Small hands and feet
• Short stature
• Poor sexual development
• Mental retardation
• Voracious appetites (usually
obese)
• Mutation is always inherited from
father
• (deletion in long arm of
chromosome 15)
Angelman Syndrome
• Exhibit frequent laughter
• Uncontrolled muscle movement
• Large mouth
• Unusual seizures
• Mutation is always inherited from
mother
• (deletion in long arm of
chromosome 15)
When does X-inactivation take place in humans?
First few weeks of development
Relate number of X chromosomes to various phenotypes discussed in lecture and to Barr body formation.
- Murray Barr (1949) discovered the Barr body.
- Mary Lyon (1961):
- Proposed that the Barr body = inactive X chromosome
- Lyon hypothesis
- X-inactivation is an example of dosage compensation and provides equal
- expression of X-chromosome products in both males and females.
*
When does X-inactivation take place in humans?
First few weeks of development
What role does Xist play in X-inactivation?
X inactivation takes place in humans during first few weeks of
development:
- • Once the X chromosome is inactivated, it remains inactive in all descendants of the first cell.
- • X inactivation is brought about by the action of Xist (X inactivation specific transcript):
- • Located on X chromosome
- • Produces an RNA molecule that coats the X chromosome and induces X inactivation.
- • Coating the X chromosome with Xist RNA causes:
- • Removal of acetyl groups from histone proteins
- • Methylation of histones
- • Alteration of histone composition
- • Pseudoautosomal region escapes inactivation
Describe the Barr body and numbers in normal male and female individuals and in individuals with abnormal numbers. Relate this to chromosome number in humans.
Females should have 1 bar body because one of there x chromsomes have been inactivated.
Male should have none because they have no extra X chromosomes to inactive
If there are any extra bar bodies avalible they indicate presence of multiple
What tissue from the implanting embryo directly interfaces with the endometrial connective tissue?
syncytiotrophoblast
Identical twinning is made possible by what process or property of the early embryo?
Regulation
List functions of the zona pellucida.
prevents premature implantation of the cleaving embryo
Describe the trophoblast and relate to its two main divisions. Which division directly interfaces with the endometrial connective tissue?
Trophoblast separates into a cellular cytotrophoblast (closest to inner cell mass) and a multinucleated syncytiotrophoblast (closest to the endometrium).
Describe the process of implantation.
Begins Day 6 after fertilization
Stages:
- Attachment of expanded blastocyst to the endometrial epithelium.
- Penetration of the uterine epithelium.
- Invasion into the tissues underlying the epithelium.
- Erosion of the maternal vascular supply
What is the most common site for ectopic pregnancy?
Ampulla
Describe the decidual reaction and its function(s).
The decidual reaction is the response of the endometrial stroma cells to the invading blastocyst. The result of the decidual reaction is a massive cellular matrix that completely surrounds the embryo and fills most of the endometrium.
A primary function of the decidual reaction is to provide an immunologically privileged site to protect the developing embryo from being rejected.
Which signaling pathway is often involved in lateral inhibition?
- Type of signaling between a dominant cell and neighboring cells
- Dominant cell refers to a cell in a population that begins to differentiate along a particular path.
- Dominant cell expresses Delta signaling molecules on its cell membrane.
- Delta then binds to Notch receptors on neighboring cells and, via the
- Delta-Notch pathway, represses genes in the neighboring cells.
Which signaling pathway is often utilized by TGF-β?
Receptor kinase pathway
Describe loss-of-function and gain-of-function mutations and give examples.
Loss-of-function mutations:
- Result in posterior to anterior transformations
- ex: antibody with XIHBOX 1 protein has been inhected into an early frog embryo and ahs prevent expression of a protein causes transformation of the anterior spinal cord
Gain-of-function mutations:
- Result in anterior to posterior transformations.
Describe functions of the egg-polarity, gap, pair-rule, segment polarity, and homeotic genes in Drosophila.
- eggpolariy
- in the establishment of the dorsal ventral and anterior-posterior axes in the fruit fly
- Genes that establish dorsal ventral axis
- dorsal, cactus, toll
- Genes that establish anterior posterior axis
- bicoid, nanos, hunch back
- Gap genes
- delete adjacent segments
- Pair rule genes
- Delete same part of pattern in every other segment
- Segment polarity
- genes affect polarity of segment
What signaling factor family is related to the segment polarity molecules in Drosophila?
- Anterior-posterior gradient:
- Anterior-posterior gradient established by Wnt-8
- Analogous to segment polarity gene (Wingless) in Drosophila
- Anterior-posterior gradient established by Wnt-8
Describe the interrelationships among the Dorsal protein, Cactus protein, and Toll protein in establishing the dorsal-ventral axis of Drosophila.
- dorsal protein
- is expressed in the ovary
- Cactus protein
- is also expressed in the ovary and binds to the dorsal protein and traps it in the cytoplasm
- Toll protein
- is expressed in the ovary and leads to degradation of cactus protein allowing the dorsal protein to move into the nuclei of the ventral cells
Describe the MiRNA pathway and its components.
- Has 2 groups, Piwi-interacting RNA’s (piRNA) that act during gametogenesis and endo-siRNAs that are expressed throughout development 2. Dicer cleaves the miRNA and the AGO loading protein goes and loads it into the target (THESE ARE IN RED IN LECTURE)
Which genes in Drosophila play a role in the establishment of the anterior-posterior axis?
Genes that establish anterior posterior axis
- bicoid, nanos, hunch back
Zinc-finger transcription factors are associated with which gene family?
Sox genes (includes the sry gene)
WT1
What is a morphogen?
A protein that varies in concentration and causes different developmental responses as a result of the concentration differences is called a morphogen
What are bottle cells and what role do they play in gastrulation?
Active cellular movement in gastrulation where groups of cells isolated from different regions of the gastrula undergo movements they would have accomplished in situation.
What are the two major signaling molecules that play a role in the formation of the primitive streak?
Nodal and Wnt
What tissues are derived from the hypoblast?
Extraembryonic endoderm and yolk sac endoderm
What tissues are derived from the epiblast?
AMniotic ectoderm
embryonic epiblast
- embryonic ectoderm
- Neural crest
- Primitive streak
- extraembryonic mesoderm
- embryonic mesoderm
- notochordal process
- embryonic mesoderm
- allantoic endoderm
When does gastrulation occur in humans?
Answer: Occurs in humans at the end of the second week of gestation
- At this stage, embryo consists of two flat layers of cells
- Epiblast
- Hypoblast
What factor represents the first sign of asymmetry in the mammalian embryo?
First sign of asymmetry involves the beating of cilia around the primitive node
Asymmetrical beating results in a directional current and expression of TGF-Beta molecules:
- Nodal: Symmetry breaking molecule in the left side of the embryo
- Lefty-1: left side of the primitive streak
Asymmetrical current occurs Bowen 2 & 6-somite stage in mouse
Name the three classical markers of the organizer region in many vertebrates.
Chordin, Gossecoid, and Fox-2
Describe the results to neurulation that would be caused by the absence of the planar cell polarity pathway.
In the absence of the PCP pathway, neural folds remain far apart and neural tube closure is absent
Which signal molecule is expressed by the isthmic organizer?
Releases Wnt-1 anteriorly and FGF-8 posteriorly
Induce gradients of En-1 (anteriorly) and En-2 (posteriorly)
Know which of the Drosophila genes involved in symmetry of the early embryo are derived from the maternal genome (maternal effect genes) rather than the embryonic genome.
- Egg polarity genes are maternal effect genes
- segmentation genes are not maternal genes
- gap genes, pair rule genes, and segment polarity genes
- Homeotic genes are not maternal effect genes
- antennapedia complex (hox)
- Bithorax complex (hox)
Describe the MiRNA pathway and its components.
no idea. I never found it
