Reproduction Lectures 2021 - FERTILIZATION & SEX DETERMINATION Flashcards
Conception can only take place in a…
limited window
Conception
union of sperm & egg
Conception usually takes place in the…
distal portion of the fallopian tube (fav. envir. for dev. –> small area, so nutrients can be transported quite quickly & easily during early dev.)
Sperm can reach the oocyte within…
30min following intercourse, but can also survive for up to 5 days in the female reproductive tract
What happens if the egg is not fertilized?
it will disintegrate & absorb through phagocytic mech’s
Why is 10’s of millions of sperm ejaculated?
to promote the possibility of fertilization
- & b/c you lose ~97% in the ejaculate already & end up with only 0.001% in the fertilization site
Where is the fertilization site?
upper third of oviduct
Sperm will 1st appear within the…
cervical canal - within 1-3 mins after ejaculation
Female repro. tract also aids in the union of sperm & egg:
- Sperm complete capacitation in the female repro. tract
- become fertile when released into the female repro. tract - Sperm movement from cervical canal –> fallopian tube, aided by a variety of aspects within female repro. tract
Sperm travel aided by:
Estrogens “thinning” cervical mucous, estrogens stimulating cervical and oviduct contraction - oxytocin, chemotaxis, thermotaxis
Describe how sperm travel aided by estrogens “thinning” cervical mucous
Shortly after ovulation, estrogens will target the mucus within the female repro. tract & they thin that mucus such that it aligns with the cervical & the cervical fibres to form channels - through which sperm will swim
The channels formed within the cervical canal are…
an identical dimension that allow sperm to swim & also increase the forward motion of that sperm movement
- additionally, the fibres will resinate at similar frequencies to the beating of the sperm flagella, promoting movement of sperm up through the repro. tract
What happens to the channels if the flagella is beating irregular?
those fibres won’t resinate & therefore irregular swimming is inhibited/movement of sperm that display a regular swimming is inhibited
- but still can make it to the fallopian tube (dead sperm can make it to the fallopian tube at same time as live sperm) –> enhances/solidifies the notion that there is mech’s within the female repro. tract that promotes sperm movement through female repro. tract
Oxytocin
released in males & females during the repro. act
Chemotaxis
cells will follow a chemical gradient
- research on frogs - where the egg releases allurin (allures the sperm to the egg)
- sperm will follow this gradient (highest concen. is at the egg - site of fertilization)
- notion that egg in females might release a chemical - that there is a gradient that sperm will ultimately follow (may only apply to fallopian tube - all depends on timing of fertilization, post ovulation)
Thermotaxis
- temp. gradient b/t cervical canal, vagina & up to the fallopian tube
- small gradient that may facilitate the movement of sperm towards the egg
Acrosomal reaction
- once sperm get to egg, they have to complete the acrosomal rxn to fertilize the egg
- proteins involved are extrem. species specific!
Describe the 4 steps of acrosomal reaction
• Acrosomal enzymes allow sperm to “drill” through the corona radiata and zona pellucida (2 layers on ovulated egg)
• Fertilin on the sperm membrane binds to integrin on the oocyte surface
- highly species specific!
- Induces a change in the oocytes membrane which blocks polyspermy
- On entry into the cell the sperm release NO which induces a release of stored Ca2+ and this is believed to initiate the final meiotic division in the oocyte
Polyspermy
multiple sperm releasing their contents into a single egg
- don’t want this to happen
- won’t fully dev.
Release of acrosomal enzymes that allows for…
the degradation of the cell membranes
Egg-binding protein
facilitate the binding & movement of sperm head through those cell layers
Fertilin & Integrin…
species specificity of fertilizing the egg
What does it mean for a sperm cell to be capacitated?
means it is fully fertile & req’s full capacitation before it is capable of fertilizing the egg
Is the haploid genome the only thing that the sperm delivers to the egg?
Absolutely NOT
Also may deliver:
- prostaglandins
- nitric oxide
- calcium
- sperm will also deliver RNA into the egg that will insist in early stages of dev.
- mitochondrial DNA –> debated (if in paternal too - most say no, strong evidence suggest that paternal mitochondrial DNA is tagged by ubiquinone & degraded, so it plays no role in further dev. of that organism (mech’s are still not explained)), vast maj. of mitochondrial DNA that is expressed in the dev. oocyte embryo & subsequent offspring is maternal
Zygote formation - syngamy
syngamy - merging of 2 haploid genomes
once that sperm has entered the egg & deposited that DNA, we get the zygote formation
Where does the zygote formation - syngamy process normally take place?
in fallopian tube & the zygote will remain in the fallopian tube (restricted area - small, nutrient rich environment so cells can divide & the blastocyst is formed typically within the fallopian tube - then is transported down the fallopian tube into the uterus)
Twins
- Occur in about 1 of every 80-90 pregnancies
- Dizygotic or fraternal twins are the result of fertilisation of two oocytes
- Monozygotic twins or maternal twins are the result of the early embryo dividing in two
- Conjoined (surgically separated later in dev.) or Siamese twins (1st identified in the formal siam)
Dizygotic or fraternal twins are the result of…
fertilisation of two oocytes
Monozygotic twins or maternal twins are the result of…
the early embryo dividing in two
Morula to blastocyst facts
- After about the third day of fertilisation – approximately 32 cells - morula
- Inner cell mass will develop into the embryo
- balstocyst supports the cells dividing at the pole during intrauterine life
Morula to blastocyst process (5 steps)
- Ovulation
- Day 1: Fertilization
- Days 2-4: Cell division takes place
- Day 4-5: Blastocyst reaches uterus
- Days 5-9: Blastocyst implants
Occasionally we’ll get ectopic pregnancies, where…
the egg is fertilized within the abdominal cavity (v. v. rare)
- won’t go to term b/c architecture isn’t there to support that but it can dev. & could be fetal to the female
Ectopic tubule pregnancy
within fallopian tube
- zygote starts to dev. in the blastocyst & doesn’t get transported down into the uterus, but rather it gets stuck in the fallopian tube
- can result in fatality if not arrested & will typically not result in a successful pregnancy
Trophoblast
protects the inner cell mass as they are dividing & that’s ready for implantation (surface layer of cells of the blastocyst)
- typically within 5-9 days of fertilization this is ready for that implantation
Inner cell mass
- will continue to divide & multiple into an embryo & ultimately fetus & ultimately birth of an individual (ultimately forms the embryo & subsequent further dev.)
- filled with embryonic stem cells - peripone/peritoneal? cells that will differentiate into any manner of diff. cells
- part of that necessary part of dev. process
Implantation of the blastocyst
once that blastocyst has reached the endometrial lining, we have implantation
Implantation of the blastocyst process
The blastocyst adheres to the endometrium and cells in the trophoblast extend and begin to digest the surrounding endometrium
Trophoblast remains…
intact as it protects that inner cell mass
Trophoblast includes cells like:
- Syncytiotrophoblast
- Cytotrophoblast
v. imp. in terms of degrading the endometrial lining
Syncytiotrophoblast
release protease’s - will degrade & breakdown the endometrium lining
Cytotrophoblast
only embryonic tissue come into direct contact with mother
During implantation of the blastocyst, the trophoblast stimulates PG (prostaglandin) release:
– Angiogenesis
– Oedema
– Improved storage
= endometrial decidua
Angiogenesis
creation of new blood vessels
Oedema
gathering of fluid
Improved storage
for nutrient transport into the developing embryo region
Endometrial decidua
the degrading/degraded endometrial lining in which the blastocyst is submerged
- lot of blood vessel growth
- collection of fluid
- & improved storage within that area
- to promote nutrient transfer & removal of waste from the developing embryo
Syncytiotrophoblast & Cytotrophoblast…
starts to degrade the endometrium lining & create a fav. environ. for further dev. of that developing embryo & ultimately fetus
The trophoblast will continue to digest endometrial cells until…
the placenta develops
@ this stage, the trophoblast is entirely engulfed by endometrial lining
The trophoblast will continue to digest endometrial cells until…
the placenta develops
@ this stage, the trophoblast is entirely engulfed by endometrial lining
Formation of the placenta
- ~12days the embryo is completely embedded and the trophoblast is 2 cell layers thick – chorion
- Chorionic villi project into the endometrial spaces filled with maternal blood
- Villi contain embryonic capillaries
- Interlocking maternal (decidual) and fetal (chorionic) tissue = placenta
Chorion
will continue to degrade the endometrial decidua & blood from the maternal side leaks into that area, providing a nutrient rich environ. for the dev. of that embryo
- within 5 weeks there should be a dev. heart within that developing embryo
The placenta during EARLY dev. within the embryo:
will act as lungs, kidney & digestive system
- much later on in fetal dev. where the fetus has sufficiently dev. tissues that it can support its own life in the absence of the role the placenta might play, the fetus takes over that at birth
With the placenta, there is NO…
blood mixing
Intertwinning b/t decidual derived (maternal) & fetal derived (chorionic blood vessels), & transfer of…
gas & nutrients will occur
With the placenta, there IS…
transfer of chemicals/molecules
- placenta can’t prevent movement of everything
- HIV can cross the placental barrier
Fetal Alchohol Syndrome
pregnant moms who are struggling with addictions may impact the dev. of the child & phenotypes as a result of FAS
- usually, impaired brain dev. but still functional individuals
Sex determination in the developing embryo
- Each nucleated cell in the human body has 46 paired chromosomes – diploid (except secondary spermocytes and oocytes - haploid)
- 22 pairs of autosomes and 1 pair of sex chromosomes – X and Y
- Karotype
X and Y
imp. components that will determine the fate/determine the fate/determination of the sex of the child born
X chromosome is ________ than Y chromosome
BIGGER
X chromosome is bigger:
- dominant alleles
- maternally derived conditions (heritable traits from the mother)
- X linked mutations
Conseq. of the X chromosome being bigger
may be a # of genes expressed on the X chromosome that are not on the Y chromosome that become these dominant alleles (not expressed in males)
X linked mutations ex’s:
- red/green colour blindness (v. common in males)
- hemophilia - inability to appropriately clot blood
- muscular dystrophy
Karotype:
chromosome type within the individual
Karotype (LIST THEM):
– XXY – viable - Klinefelters syndrome – infertile adult males
– XYY – viable – no real side effects (super males)
– YO – not viable (NOT REACH TERM & BE ABORTED)
– X0 – viable - Turners syndrome – usually infertile adults
Many populations have an operant sex ratio…
often times in wild animals it is 1:1 (female: male)
- sometimes becomes skewed
In females, at fertilization, the sex ratio is:
& @ birth
120 males: 100 females
@ birth: 105 male: 100 females
therefore, male have higher potential of NOT reaching term
Genotypic sex potential
- For the first 6-7 weeks XY embryo’s have the potential to go either way - bipotential
- The sex determining region on the Y chromosome expresses the SRY gene in cells on the urogenital ridge
- Stimulates the production of the protein H-Y antigen which directs the development of the male gonads
- Females of course lack the Y chromosome and therefore lack the SRY gene
Bipotential
sex is undetermined & the sex region on the Y chromosome is what ultimately will drive an individual toward a female or male karotype
Where will external genitalia develop from?
External genitalia will develop from the same undifferentiated tissue
FEMALE Reproductive tract develops from…
Müllerian ducts
MALES Reproductive tract develops from…
Wolffian ducts
Describe female development of external genitalia
Bipotential stage (6 week fetus) 1st
In the ABSENCE of androgens, the external genitalia are feminized
Describe male development of external genitalia
Bipotential stage (6 week fetus) 1st
- DHT causes development of male external genitalia
- The testes descend from the abdominal cavity into the scrotum
Dihydrotestosterone (DHT) is imp. for…
the dev. of male external genitalia
Describe male sex determination process
- Ovum with X chromosome
- Fertilized by sperm with Y chromosome
- Embryo with XY chromosome
- SRY stimulates production of H-Y antigen in plasma membrane of undifferentiated gonads (in the urogenital ridge)
- H-Y antigen directs differentiation of gonads to testes
- Testes secrete Mullerian-inhibiting factor
1st direction:
- testosterone –> wolffian ducts develop into the male reproductive tract
- DHT
- promotes development of undifferentiated external genitalia (penis, scrotum etc)
2nd direction:
- Mullerian-inhibiting factor
- degeneration of Mullerian ducts
Describe female sex determination process
- Ovum with X chromosome
- Fertilized by sperm with X chromosome
- Embryo with XX chromosome
- No Y chromosome, no SRY no H-Y antigen
- No H-Y antigen undifferentiated gonads develop into ovaries
- No testosterone or Mullerian inhibiting factor
1st direction:
- absence of Mullerian-inhibiting factor
- Mullerian ducts develop into the female reproductive tract
2nd direction:
- absence of testosterone –> degeneration of Wolffian ducts
- promotes development of undifferentiated external genitalia (clitoris, labia, etc)
5 alpha reductase
imp. enzyme req. to convert testosterone –> DHT
What if 5 alpha reductase is not expressed to appropriate levels?
you get insufficient levels of DHT produced
- as a conseq. of that, it’s possible (pretty rare) that that red. in DHT leads to retardation in the promotion of male genitalia & as a conseq. female genitalia can be expressed (not to the same extent, but can persist all the way to birth)
- when puberty happens, you get that massive influx of testosterone & further growth of the male genitalia
- as a result of 5 alpha reductase activity
Intrauterine Position Effect
• rats & mice have bicornate uterus
– developing fetuses arranged sequentially in uterine horns
– each in its own amniotic sac with its own placental connection
• secretions of fetal endocrine glands alter the morphology, physiology & behaviour of neighbours
Bicornate uterus
uterus split in 2
- have developing fetuses neighbouring each other in that uterus
Describe the Intrauterine Position Effect in terms of the types of females and the result
• 3 types of females – 0M,1M,2M
• by 17 d gestation, males have 3x the testosterone of females (& there can be spill over from the males into the female compartment & such that)
• female fetuses are “contaminated” by testosterone from male neighbours
– 2M>1M>0M
hormones pass via uterine blood vessels to neighbouring fetuses can masculinise females
1 M
neighboured by a single male developing fetus
2 M
2 male neighbours during dev.
0 M
neighboured by another female
2 M females are…
masculinased & do exhibit more male type behaviour (tend to be more aggressive for ex)
Fraternal Birth Order (FBO) Effect
- each male developing in utero increases the probability of subsequent male being gay
- not attributable to environmental effect
- stepbrothers in home don’t produce effect
- biological brothers reared apart produce effect
Fraternal Birth Order (FBO) Effect is potentially explained by “maternal immunization hypothesis”
– mother carrying first son has little exposure to male proteins due to placental barrier (particularly Y-coded)
– mixing of fetal and maternal blood AT DELIVERY causes female immune response to male proteins (antibodies produced)
– subsequent sons are exposed to these antibodies which attack male-specific proteins, thereby altering development and increasing probability of male being gay
Fraternal Birth Order (FBO) Effect only applies to…
right-handed males
- probably something to do with the right/left hemispheres of the brain
Each previous male increases the probability of the next male to by gay by…
one-third
- so if you’re the 5th male born, it’s almost certain that that individual may be gay
