embryo ch 2 and 3
GENE EXPRESSION AND DIFFERENTIATION
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Gene expression regulated by
o Different genes transcribed
o DNA transcribed from gene selectively processed to regulate which RNAs become mRNA
o mRNAs may be selectively translated
o proteins made from mRNAs differently modified
linker DNA – part of DNA linking that looped around histones – joins two nucleosomes
promoter region binds RNA polymerase for initiation of transcription
3’ end has poly-A tail – 5’ end has TATA box
Enhancers – regulatory elements of DNA that activate utilization of promoters to control
efficiency and rate of transcription
Nuclear RNA – nRNA – mRNA before introns come out
Spliceosomes – snRNA that recognize and splice nRNA
Splicing isoforms – proteins derived from same gene due to different splicing
Competence – ability of responding tissue to respond to induction
Paracrine interactions – proteins synthesized by one cell diffuse over short distances to interact
with next cell
Juxtacrine signaling – neighbor cells signal by touch, ligands in extracellular matrix secreted by
one cell interact with another cell on matrix, or signals travel via gap junctions
Paracrine signaling factors – also called growth and differentiation factors (GDFs)
o Fibroblast growth factors (FGFs) – used for angiogenesis, axon growth, and mesoderm
differentiation
o Hedgehog proteins – desert, Indian, or sonic
 Sonic hedgehog is involved in limb patterning, somite differentiation, and gut
regionalization
o WNT proteins – frizzled family of proteins – limb patterning, midbrain development,
some aspects of somite and urogenital differentiation
GAMETOGENESIS
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Gametes derived from primordial germ cells (PGCs) formed in epiblast during 2nd week
Germ cells undergo gametogenesis in preparation for fertilization – cytodifferentiation finishes
it
Teratoma – tumor in fetus or created by fetus that contains random parts of random tissue
(hair, teeth, skin, gut, etc.)
Linked genes – genes on the same chromosome
Synapsis – metaphase I of meiosis
Chiasma – structure of crossed chromosomes formed by crossing over
35 years of age and up in woman increases nondisjunction
GENETIC DISORDERS
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Down Syndrome – trisomy 21
Trisomy 18 – intellectual disability, congenital heart defects, low-set ears, malformations of
skeletal system – die very early (85% aborted spontaneously)
Trisomy 13 – intellectual disability, eye and ear defects, cleft lip and palate, heart defects (90%
die in first month after birth)
Klinefelter syndrome – XXY
Turner syndrome – only monosomy compatible with life – XO – 98% of these fetuses are
spontaneously aborted – mostly caused by nondisjunction in male – no gonads at all
Tripe X Syndrome – XXX – often go undiagnosed – often have speech problems – two Barr
bodies
Cri-du-chat Syndrome – deletion of short arm of chromosome 5 – small head, heart problems,
intellectual disability, and cat-like cry
Angelman’s syndrome – microdeletion on long arm of chromosome 15 – intellectual disability,
cannot speak, poor motor movement, laugh for no reason – DELETION ON MATERNAL GAMETE
Prader-Willi syndrome – microdeletion on long arm of chromosome 15 in PATERNAL GAMETE –
obesity, intellectual disability, hypogonadism, hypotonia
Miller-Dieker syndrome – deletion at 17p13 (first number is chromosome number, p for short
arm or q for long arm, second number is gene number) – cardiac and facial abnormalities,
developmental delay, seizures, lissencephaly (no cerebral folds)
Fragile sites – regions of chromosomes with propensity to break or separate
Fragile X syndrome – repeats of promoter region in Xq27 – intellectual disability, large ears,
prominent jaw, large testes – second to Down syndrome as cause of intellectual disability
OOGENESIS
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Oogenesis – once PGCs arrive in gonad of genetic female, they differentiate into oogonia
Several mitotic divisions make oogonia become cluster of primary oocytes surrounded by
epithelial cells (follicular cells) that originate from surface epithelium covering ovary
Primary oocytes are arrested in prophase I and don’t continue until puberty
Diplotene stage – resting stage during prophase characterized by lacy network of chromatin –
held here by oocyte maturation inhibitor (OMI)
Fewer than 500 oocytes are actually ovulated
Each month, 15-20 follicles mature – some die before full maturity
o These follicles accumulate fluid in the antrum
o Essentially a race to the first to reach maturity
Graafian follicle – mature vesicular follicle
LH induces preovulatory growth phase when secondary follicle matures
Polar bodies accumulate between zona pellucida and PM of secondary oocyte
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Oocyte arrested in metaphase II during ovulation and only completes if cell fertilized –
degenerates about 24 hours after ovulation if not fertilized
SPERMATOGENESIS
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Begins at puberty
Type A spermatogonia  Type B spermatogonia  primary spermatocytes  secondary
spermatocytes  spermatids  spermatozoa
Epithelium surrounds forming sperm – sustentacular cells (Sertoli cells)
FSH – binds to Sertoli cells and stimulate testicular fluid production and synthesis of intracellular
androgen receptors
Spermiogenesis – process of spermatid becoming spermatozoa
o Formation of acrosome
o Condensation of nucleus
o Formation of neck, middle piece, and tail
o Shedding of most of cytoplasm as residual bodies
About 300 million sperm produced daily
Sperm obtain full motility in epididymis
Spermatocytogenesis is process from spermatogonia to primary spermatocyte
OVULATION TO IMPLANTION
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Gonadotropin-releasing hormone (GnRH) – produced by hypothalamus and signals anterior
pituitary to release gonadotropins (FSH and LH)
Corpus atreticum – connective tissue comprised of degenerating follicle and oocyte
FSH stimulates follicles to grow and leave “egg nest” of primordial follicles
o These become primary follicles
o FSH also stimulates maturation of granulosa cells surrounding oocyte
Theca interna cells produce androstenedione and testosterone – granular cells convert these to
estrone and 17β-estradiol
Estrogens produced by granular cell conversion cause
o Uterine endometrium to enter follicular (proliferative) phase
o Thinning of cervical mucus to allow sperm passage
o Anterior lobe of pituitary gland stimulated to secrete LH
Midcycle, an LH surge
o Elevates concentrations of maturation-promoting factor, causing oocytes to complete
meiosis I
o Stimulates production of progesterone by follicular stromal cells (luteinization)
o Causes follicular rupture and ovulation
Mittelschmerz – pain felt during ovulation
Ovulation generally accompanied by a rise in basal temperature
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Drugs can stimulate gonadotropin release to cause ovulation, but is 10x more likely to cause
multiple pregnancy
FSH and LH influence vesicular follicle to grow rapidly to become mature vesicular follicle
(Graafian) – oocyte arrested in metaphase II about 3-12 hrs before ovulation
Surface of ovary begins to bulge locally and at apex, avascular spot (stigma) appears
High concentrations of LH increase collagenase activity, digesting collagen fibers surrounding
follicle
LH surge also increases prostaglandin levels, which cause local muscular contractions in ovarian
wall to cause ovulation
Corona radiata – formed from cumulus oophorous cells that come along for the ride during
ovulation
After ovulation, granulosa cells remaining in wall of ruptured follicle and cells from theca interna
vascularized by surrounding vessels
o Under influence of LH, these cells develop yellowish pigment and change to lutein cells,
which form corpus luteum and secrete estrogens and progesterone
Progesterone – along with some estrogen, causes uterine mucosa to enter progestational
(secretory) stage
Fimbriae of uterine tube sweep over surface of ovary while uterine tube undergoes peristalsis
Once in uterine tube, cumulus cells withdraw cytoplasmic processes from zona pellucida and
lose contact with oocyte
Cilia in tubal mucosa help push oocyte along with peristalsis
If fertilization does not occur, corpus luteum reaches max development about 9 days after
ovulation
o Yellowish projection on surface of ovary shrinks because of luteolysis and forms mass of
fibrotic scar tissue (corpus albicans)
o Progesterone production decreases, precipitating menstrual bleeding
If fertilized, degeneration of corpus luteum prevented by human chorionic gonadotropin,
secreted by syncytiotrophoblast of developing embryo
Corpus luteum continues to grow and forms corpus luteum of pregnancy (corpus luteum
graviditatis)
o Continues to secrete progesterone until end of 4th month, then regress slowly as
progesterone produced by trophoblastic component of placenta takes over
o If corpus luteum removed before fourth month, fetus will most likely die
Fertilization usually occurs in ampullary region of uterine tube, close to ovary
Spermatozoa may remain viable in female reproductive tract for up to six days
Only 1% of sperm deposited in vagina reach cervix – muscular contractions of uterus and uterine
tube help them along – range in speed from 30 min to 6 days
Once at isthmus, sperm become less motile and cease migration – at ovulation, sperm become
motile again and swim to ampulla
In order to fertilize oocyte, spermatozoa must undergo:
o
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Capacitation – period of conditioning in female reproductive tract that take about 7
hours – involves epithelial interactions between sperm and mucosal surface of tube –
glycoprotein coat and seminal plasma removed from acrosomal region
o Acrosome reaction – induced by zona pellucida proteins culminating in release of
enzymes needed to penetrate zona pellucida (acrosin and tripsin-like substances)
Zona pellucida maintains sperm binding while inducing acrosome reaction – release of acrosin
by acrosome allows penetration of zona pellucida
Permeability of zona pellucida changes when head of sperm contacts oocyte PM because
contact results in release of lysosomal enzymes from cortical granules lining PM of oocyte
Zona reaction – zona pellucida going impenetrable and inactivating receptor sites on zona
surface
Initial adhesion of sperm to oocyte mediated by integrins on oocyte interacting with disintegrins
on sperm
Fusion accomplished between oocyte PM and PM covering posterior region of sperm head –
head and tail enter oocyte leaving only PM behind, causing
o Cortical and zona reactions – release of cortical oocyte granules that contain lysosomal
enzymes
o Resumption of meiosis – definitive oocyte arranges its chromosomes into female
pronucleus
o Metabolic activation of egg to initiate early embryogenesis
Male pronucleus becomes prominent and tail disintegrates
Pronuclei replicate DNA then undergo mitosis  formation of morula
CONTRACEPTIVE METHODS
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Hormonal – provide estrogen and/or progestin, inhibiting release of FSH and LH and thus
preventing ovulation, changing lining of uterus and thickening cervical mucus
Male “pill” – contains synthetic androgen that prevents LH and FSH secretion that stops sperm
production or reduces it to level of infertility
Intrauterine devices (IUDs) – T-shaped unit
o Hormonal IUD – releases progestin that causes thickening of cervical mucus – may make
sperm less active and egg and sperm less viable
o Copper IUD – releases copper into uterus to prevent fertilization or attachment of
fertilized egg to uterine wall – prevents sperm from entering uterine tubes
Emergency contraceptive pills (ECPs) – taken within 120 hours of sex
o High dose of progestin (with or without estrogen – combination with estrogen
commonly called Plan B)
o Antihormonal ECPs – i.e., mifepristone can act as abortifacient if egg already implanted
INFERTILITY
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Problem for 15%-30% of couples
Assisted reproductive technology (ART) – methods to help infertility
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In vitro fertilization (IVF) – most common method to help infertility – gonadotropins
used to bring follicle growth just shy of ovulation, then oocytes recovered via laproscopy
and put in culture medium with sperm – zygote monitored to 8 cell stage and then
placed in uterus to develop
o Chances that these work drops with age of mother
o End up in premature births and multiple pregnancies
o Often can have birth defects
Therapeutic cloning – take differentiated adult cell and introduce it to enucleated oocyte, which
is then stimulated to form blastocyst, but is completely unviable – used for more ethical stem
cell production
Oligozoospermia – very few live sperm per ejaculation
Azoospermia – no live sperm per ejaculation
Intracytoplasmic sperm injection – sperm injected into egg to cause fertilization
o Risk for Y chromosome deletions but no other chromosomal abnormalities
IMPLANTATION
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L selectin on trophoblast cells and carbohydrate receptors on uterine epithelium mediate initial
attachment
Uterus wall
o Endometrium – mucosa lining inside wall – place where fertilized egg attaches
o Myometrium – thick layer of smooth muscle
o Perimetrium – peritoneal covering lining outside wall
Endometrium undergoes follicular phase until ovulation  secretory (progestational phase) 
mensus (or implantation)
o Endometrium shed during menstruation (compact and spongy layers)
o Venules and sinusoidal spaces become packed with blood cells and extensive diapedesis
of blood into tissue occurs
o When menstruation begins, blood escapes from superficial arteries and small pieces of
stroma and glands break away
o Basal layer of endometrium remains – has its own arteries and functions as regenerative
layer to rebuild compact and spongy layers
Normally blastocyst implants in anterior or posterior wall
Day 11-12 – new cells appear between inner surface of cytotrophoblast and outer surface of
exocoelomic cavitiy – derived from yolk sac cells and form loose, fine connective tissue
(extraembryonic mesoderm) – eventually fills all space between trophoblast and amnion and
exocoelomic membrane
o Extraembryonic somatic mesoderm – side lining cytotrophoblast and amnion
o Extraembryonic splanchnic mesoderm – side covering yolk sac
Sometimes around day 13, bleeding occurs around implantation site as a result of increased
blood flow into lacunar spaces – can be confused for menses since around that time
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Extraembryonic mesoderm lining inside cytotrophoblast called chorionic plate when chorionic
cavity forms
Genomic imprinting – differential modification and/or expression of homologous alleles or
chromosome regions depending on parent they got it from