module 3- conception and implantation Flashcards
what is the best way to describe the human sexual response
the 4 phase model of sexual response cycle
what does the 4 phase model of sexual response cycle focus on
the physiological aspects of the sexual response
who formulated the 4 phase sexaul response cycle
- william H masters and virgina E johnson 1966
what is the 4 used to describe
the common physiological changes that occur when engaging in intercourse or sexually stimulating activities
phase 1: 4 phase model
excitement
- increase in arousal that results as a response to sexual stimuli
signs of phase 1
- increased heart rate
- increased blood pressure
- accelerated breathing
- increased muscle tension
- increase blow flow to genitals
phase 2: 4 phase model
plateau
- continuation or intensification of the responses observed in phase 1
phase 3: 4 phase model
orgasm
- conclusion of the plateau phase and the shortest phase, lasting only a few seconds
signs of phase 3
- involuntary muscle contractions
- peak in heart rate
- blood pressure
- breathing
- release of muscle tension
(vaginal contractions) (ejaculation males)
phase 4: of 4 phase model
resolution
- body slowly returns to its normal state
- swelled/erect body parts go back to normal
- general sense of well-being, enhanced intimacy, and fatigue
what is the sexual response mediated by for male and females
- autonomic nervous system
- somatic innervation
autonomic nervous system
- involuntary control
- divided into sympathetic and parasympathetic
somatic innervation
- nerves responsible for sensation and associated with voluntary control of muscles
what are all sexual stimuli mental or physcial integrated by
- autonomic nervous system via the spinal cord
what is the process of integration a key to
coodinate the subsequent responses and reflexes that characterize the sexual response
what does the sexual response involve
complex interplay between somatic, parasympathetic and symtpathic input
where does all the innervation for the reproduction organs originate from
- sacral (parasympathetic) and lumbar nerve roots (sympathetic) in the spine
what are the shared reflexes
- vascular dilation
- stimulation of secretions
- smooth muscle contractions
- contractions of the somatic pelvic muscles
vascular dilation
causes swelling of the genital organs
stimulation of secretions
either prostatic or vaginal secretions
smooth muscle contractions
of the vas deferns during ejaculation in males or rhythmic vaginal contraction during orgasm in femals
contractions of the somatic pelvic muscles
that accompany orgasm in both sexes
what is the first sexual stimuli for males in phase 1: excitement
erectile reflex
sexual stimuli males phase 1, how
- integrated by the central NS to stimulate the parasympathetic nerves that supply the arterioles of the penis, initiating the erection reflex
what does the parasympathetic nerve fibers release in the phase 1, males + what does that do
- neurotransmitters
- induce relaxation of the smooth muscles of the arteries of the corpora cavernosa allowing blood flow into the sinusoids of the corpora cavernosa
what does high pressure in the sinusoids cause
push against the hard sruface of the tunica albuginea and causes ballooning of the tissue
- also causes occlusion of the veins between the tunica albuginea and the peripheral sinusoids (reducing venous outflow)
- overall hardening and elongating the penis
what is the role of nitric oxide for males
responsible for inducing the relaxation of smooth muscles of the penile arteries
- NO is released from parasymtpathetic and local endothelial cells during sexual arousal
what does NO activate
guanylyl cylase within smooth muscle cells, increasing the cellular concentration of cGMP
what does cGMP activate
additional secondary messenger molecules that cause a reduction in the intracellular calcium ion concentration, leading to smooth-muscle relaxation
what enxyme can revers the effect of NO
PDE-5 by rapidly metalizing cGMP to GMP
plateu phase for males
erection reflex continues and additional changes occur
what are the additional change that occur in the plateu phase for males
- urethral sphincter contracts to prevent retrograde ejaculation
- bulbourethral glands produce mucus to aid lubrication
- scrotum may become tightened, causing the testicles to rise to the body, necessary for full ejaculation
orgasm phase 3 males what does it lead to
sudden release of semen through the penis (ejaculation)
how does ejaculation occur
- when the sexual stimuli becomes very intense, the reflex centers of the spinal cord begin to emit sympathetic impulses that lead to ejaculation (semen out the urethra via rhythmic contractions)
first phase of the orgasm phase
- emission
emission
the bladder neck closes to prevent retrograde ejaculations’
emission contrinued
- sperm mixes with prostatic fluid as they are ejacted into the prostatic section of the urethra followed by seminal vesicle fluid, and cowpers gland fluid
what is the second phase of the orgasm phase
expulsion
expulsion
rhythmic contractions are generated by the bulbospongiosus and ischiocavernosus muscles
- and seme is propelled outward
resolution phase of males what happens
- the ability to have an erection or rejactulation is inhibited temporarily (known as the refractory period)
- length of this period varies
what is the hormones responsible for the male refractory period
oxytocin
- key in ejaculation and the post ejaculatory detumescence of the penis
detumscence of the penis
the process of subsiding from a state of tension, swelling or sexual arousal
what are the 2 main categories of erectile disorders
ischemic priapism and erectile dysfunction
ischemic pripism
- penis remains erect for hours due to inadequate draining of the blood from the penis
- occurs when promblems in the resolution phase of males
erectile dysfunction
- ability to get or maintain erection is impaired
- serve causes ranging from psychogenic, neurogenic, endocrinoligic, or arteriogenic
(low arteriole pressure or high levels of vasoconstricion may suffer)
physiological changes during excitement phase for females
- swelling of external genitalia
- elevation of the uterus
- increased vaginal lubrication
- swelling of the breasts
swelling of external genitalia
- the clitoris, surrounding labia, and the vagina become engorded with blood
- innervated by parasympathetic
what does the clitoris become in the excitment phase
tumescent as its composed of vascular eretile tissue
tumescent
swollen
increased vaginal lubrication
vasocngestion of the pelvic organs results in the production of vaginal lubrication, which composed of transudate
- bartholins glands also contribute to lubrication by secreting mucus
elevation of the uterus
the uterues goes upward known as uterine tenting, causing the internal enlargement of the vaginal canal
swelling of the breasts
increased blood pressure of the excitement phase causes the swelling of the external genitalia and swelling and enlargement of the breasts
what happens to the female in the plateau phase
more pronouced:
- swelling of clit
- labia minora
- vagina increases
- uterus elevates further
- increased lubrication
- swellong of external genitalia and breasts
what happens near the moment of orgasm for women
- pubococcygeus muscle tightens
- reducing the diameter of vaginal opening
- tissues near the opening swell significantly forming orgasmic platform
what happens in a orasgma of women
- involuntary, rhythmic contractions of the uterus and vaginal muscles, particularly at the orgasmic platform, followed by release of muscle tension
what are the involuntary contractions of the uterus aiding in for females
- transporting the sperm as they jouney up the female reproductive tract to reach the oviducts
what happens in the resolution pahse for females
refractory phase (not as pronouced as males)
- females can experience multiple orgasms before or after entering the refractory period
persistent genital arousal disorder
- women become sexually aroused without any sexual activity or stimulation
- spontaneous, persistent, unwanted and uncontrollable genital arousal can be painful and distrupful to persons life
how human genitalia have coevolved
- penis largest of all primates possibly evolved to adapt to the female vagina
- as humans became bipedial the relative positions of the pelvis shifted towards down
- we grew larger heads which required wider pelvis and vaginal canal for babies
- likely that in order to stimulate both partners towards successful intercourse, the male penis also had to grow bigger
what is internal fertilization process
- occurs within the female body
- female gamete is non-motile and the male gametes motility is designed to ensure it reaches the female gamete
- howerver both gametes do need to travel a certain distance for fertilization
what is the site of fertilization
ampulla of the fallopian tube
what is egg transport
refers to the movement of the oocyte from the moment of expulsion from the ovarian follicle to its entry into the distal segment of the fallopian tube
what is the cumulus-oocyte complex (COC)
upon ovulation the oocyte is released within a thick layer of surrounding cumulus cells
what do the cumulus cells do
closely surround the occyte to produce large amounts of hyaluronan, along with other components form an expanded extracellular matrix
hyaluronan
this molecule is polysaccharide which consitiutes a large portion of the extracellular matrix
what are the functions of the cumulus layer
- aiding the pickup of the oocyte by the oviduct
- release of sperm-attracting molecules to increase the chances of an encounter with one of the few sperm that will reach the ampulla tube
what happens to the cumulus layer once sperm reaches egg
it is the first barrier that it will need to penetrate to reach the egg
stigma
the area of the ovarian surface where the follicle will burst through during ovulation and release the ovum
what is the cumulus cell layer composed of
the same granulose cells that surround the occyte inside the preovulatory or antral follicle, before the egg is released
what happens after release oocyte
- it does not immediately land insdie the fallopian tube, it must find its way
peridoic sweeping of ovarian surface by the fimbriae
allows the egg to attach and gain entry into the fallopian tube
how does peridoic sweeping work
- the beating of the ciliated cells of the oviductual epithelium, and peristalitc movements of the oviduct help transport the oocyte to the ampulla
what is the final step of transport of ova
activation of the oocyte
- only occurs at fertilization
activation of oocyte
upon sperm entry the oocyte completes meiosis II and completes its fusion with the sperm
how does a sperm achieve the long-pre fertilization jounrye
- sperm must finsih their maturation and become “activated” within the female reproductive tract via a carefully regulated multistep process that involves lots of signals from male and female
first of sperm transport and maturation
spermatozoa undergo maturational changes within the male reproductive tract
changes to the spermatozoa within the male repro tract
acquiring motility changing their membrane fluidity during their transit through the epididymis, and being coated with decapitation factors
what does the female repro tract due to contribute to maturation of sperm
- careful regulation of the rate at which spermatozoa achieve maturity so that they are delivered to the surface of the oocyte in a fully primated state, ready for fertilization
what are the major sets sperm must undergo to become activated and fertilizated
- capacitation
- acrosome reaction
activated sperm
what is a capacitated sperm
has acrosomal cap regions and equatorial region
what is sperm capacitation
is the process by which sperm acquire the capacity to fertilize
how does sperm capacitiation occur
- begins as sperm come in contact with the cervical mucus, whose acidic pH, compared to the alkalinity of semen, causes the modification of sperm surface molecules
what happens to increase sperm chances of reaching the oocyte in their optimal state
seminal fluids coat spermatozoa with inhibitory factors, collectivity termed decapacitations factors
example of decapacitation factors
cholesterol
- serves to stabilize the plasma membrane of the spermatozoa during transit in the male reproductive tract and prevent the intermolecular interactions responsible for achieving a capacitate state
what increases the chances of sperm coming across the oocyte in their optimal state
maturation in a staggered sequence
what happens to removal of the cholsesterol from the sperm plasma membrane
may be initiating event for capcitation
what does albumin from female secretion to
binds cholesterol, causing the outer acrosomal membrane (of sperm) to have increased permeability and fluidity as a result of these changes
why does permeable sperm allow
for the influx of calcium and bicarbonate,
what does the influx of calcium and bicarbonate result in
activation of second messengers and inhibition of signaling events that will later facilitate the acrosome reaction
what does capactitation also involve
hyperactivation
what is the hyperactivation of sperm
- flagellar wave pattern of the sperm changes to asymmetrical and faster thrashing of the sperm tail (help propel sperm forward)
how does a sperm get hypermotility
- cumulus cells (of oocyte) release progesterone
- that binds to Ca ions channel (catsper) on the surface of flagella
- this binding acitvations the Ca channel and stimulates hypermotility of the tail towards occyte
what does progesterone also do to the sperm
acts as a chemoattractant molecule that helps guide the sperm towards the oocyte
what is the acrosome reaction
is an exocytotic process occurring in the sperm head that is essential for penetration of the zona pellucida and fertilization of the oocyte.
the induction of acrosomal exocytosis
occurs when spermatozoa approach the oocyte in response to soluble factors in the vicinity of the cumulus-oocyte complex such as progesterone
exocytosis
process in which the cells transport molecules out of the cell
what does the acrosome reaction begin
begins after the sperm traverses the cumulus layer and reaches the zona pellucida
is the female tract welcoming to sperm
no.
- most spermatozoa released during ejaculation are elminated from the female tract through the same mechansism deisgned to defend female tract from pathogens
does the female tract have mechanisms to facilitate transfer of sperm
yes around ovulation
what are mechanisms to faciliate the transfer of sperm
- cervical mucus and muscle contraction
- oviductal fluid
cervical mucus and muscle contraction
- around time of ovulation, the ceervix opens up to facilate sperm entry
- the mucus becomes thinner due to the high levels of estrogen, which helps the sperm swim towards the oocyte
- the muscle contraction also help transport sperm
oviductal fluid how is it produced
by the oviductal epithelium
how does the oviductal fluid help transport sperm
the epithelium that produces it alwasy flows in the direction of the uterus because of the beasting of the oviductal cilia
- the egg and chemoattractant molecules that indicate the position of the egg are pushed toward the incoming sperm
after fertilization and oviductal fluid
the flow will help transport the zygote towards the uterus
what is the timing of fertilization
- an oocyte is viable for approx. 24-48h (small window after ovulation during which fert can occur)
how long can sperm survive in female tract
3-5 days, meaning they cane be present a few days before ovulation and manage to fertilize an oocyte once its released
(most common for fert to occur this way)
where is the site of fert
in the oviduct, specifically the ampulla of the fallopian tube
how many steps in fertilization
4
1. binding and penetration of cumulus matrix
2. adhesion and penetration of zona pellucida
3. plasma membrane fusion
4. oocyte activation and nuclear fusion
step 1: of fert
- sperm cells make contact with the outer layer cumulus cells (penetration requires mechical and chemical forces)
what makes contact with the cumulus layer
hyperactivated sperms
what comes into contact with the hyaluronan molecule in the extracellular matrix of the cumulus
hyalurondiase protein in the sperm head
what does the hyaluronidase protein in sperm head coming into contact with the hyaluronan molecule created
degrading the molecules allowing sperm to transverse the cumulus layer and reach the zona pelluica
what is the penetration of the zona pellcuida a key step for
allowing sperm to gain access to the oocyte
- however before penetration occurs the sperm must first bind to the zona pellucida
how does sperm interact with the zona pellucida
zona binding
acrosome recreation
what is the zona binding
- after crossing the cumulus layer, spermatozoa reach the zona pellucida
zona binding: after crossing the cumulus layer
the plasma membrane of the sperm head then binds tightly to this membrane, in a step known as zona binding
what is the zona pellucide
is an extracellular matrix composed of 3 glycoproteins: ZP1, ZP2, ZP3
what do the receptors on the sperm plasma membrane attach to
ZP3, which triggers the sperm head to undergo the acrosome reaction
what does the acrosome reaction involve
the fusion of the plasma membrane with the outer arcosomal membrane of the sperm
what does the acrosome reaction cause the release of
enxymes (including neuroaminidsae and acrosin) from the acrosomal space of the sperm to break down the zona pellucida
neuraminidase
an enzyme, present in many pathogenic or symbiotic microorganisms, that catalyzes the breakdown of glycosides containing neuraminic acid
acrosin
a proteolyic enzyme found in the acrosomes of spermatozoa, that enables penetration of the egg
what does the enxymes help with in the acrosome reactions
breaking down the zona pellucide allowing the sperm to reach the vitelline membrane of the oocyte
what does the acrsome reaction expose
the inner acrosomal membrane with its receptors for another zona pellucida gylcoprotein, ZP2
step 3: of fertilization ,
plasma membrane fusion
what happens after zona binding and acrosome reaction
sperm penetrate the zona and enter the perivitelline space
perivitelline space
the extracellular region between the zona pelluida and the oocyte plasma membrane where the final adhesion in the fertilizaition process occurs
plasma membrane fusion: the inner acrosomal membrane
binds to the oocyte membrane via the ZP2 receptors ,which mediates fusion of the plasma membrane of the sperm to that of the ovum
what happens to the sperm when it fuses with the ovum
the sperm head loses the tail and only the sperm head is incporated into the ovum
what does the oocyte deply upon fusion
deploys 2 mechanisms to prevent polyspermy, which is penetration by more than one sperm
what are 2 mechanisms used to prevent polyspermy
fast block
cortical reaction (slow block)
what does fast block involve
a near instantaneous change in sodium ion permeability up on binding of the first sperm, depolaring the oocyte plasma membrane and preventing the fusion of additional sperm cells.
when does the fast block occur and more how long
- sets in almost immediately and last for about a minute, during which time an influx of calcium ions following sperm penetration triggers the second mechanism, the slow block
what is cortical reaction
referred to as the process cortical reaction, cortical granules sitting immediately below the oocyte plasma membrane fuse with the membrane and release zonal inhibiting proteins and glycosaminoglycans in the periviteliine space
what does the release of zonal inhibiting protein and glycosaminoglycans cause
cause the release of any other attached sperm and destroying the oocyes glycoportieints (located on the zona pellucida), thus preventing any more sperm binding to these receptors
step 4 of fertilization: occyte activation and nuclear fusion what does it involve
oocyte activation, in which the egg resumes and completes meiosis II and the pronuclei of the oocyte and sperm now fuse, creating a zygote
what nutrient is involved in egg activation
zinc
what does zinc do in egg activation
it is required in high levels for meiotic progession of the egg
what must zinc do after after fert
decrease for cell cycle resumption so there is coordinated release of zinc into the extracellular space in a prominent ‘zinc spark’
after fertilization what happens with the gametes
undergo a transition step invovling massive modification to the parental cell structure
what do the partental genomes do after fert
fuse and the genome is reprogrammed to switch from a highly speciliazed cell to a totipotent cell
totipotent cell
capable of giving rise to any other cell type in the body
what is also altered after fert with the parental genomes
cell cycle machinery is reprogrammed to switch from meitoic to mitotic division, thus transiting from gamate to zygote and initing the process of embyro development
what happens after release of ovum
transported to the ampullary-isthmic junction where fertilization takes place
what happens after fertilization/ wehre does embyro go
needs to travel from the oviduct to the uterus and succeed in implanting itself onto the uterine surface
what is the preimplantation period
the period of time between ferilization and the moment of embryo attachment
- take 8-10 days
what is cleavage and when does it occur
between day 0 and day 8
- are rapid cell divisions that will lead to tissue differentiation, but with no significant growth
what does cleavage division result in?
cell cluster that are the same sizes as the orginal zygote
what are the resulting cells from cleavage called?
blastomeres
day 1 of cell divisions of the preimplantation period
first cleavage
what happens in first cell cleavage
the number of cells doubles with each cell division, starting with the zygote dividing into 2 cells
what is the 2-cell stage of the embryo
the zygote dividing into 2 cells
- the embryo has 2 evenly sized blastomeres each containing 1 nucleus
day 2-4 of cell divisons of the preimplanatation pe4riod
further cleavages
what happens in day 2-4 preimplanataion perid
the number of blastomeres will double with each division, causing the 2-cell embryo to dividion into 4 cells, 8cell and then 16 cells
what happens at the 16 cells stage
the embryo is also known as the morula
day 4 of the preimplanatation period and cell divison
compaction
what happens in compaction
in the morula, the cells begin to exert pressure against each other, mainly because they are still encased within the zona pellucida layer
- bc the pressure inside the embryo increases the cells undergo compaction, becoming deformed and flattened
day 5 of preimplanation period
blastulation
what happens in blasutlation
the process of compaction provides cells with signals that induce them to differentiate into inner and outer cells
what does differentiate into inner and outer cells induce
the formation of the blastocyst from a morula, which is the process of basculation
inner cell : blastocyst
it will later form the trilaminar germ disc, undergo gastrulation and then form the fetus so the inner cell mass is also known as the embryoblast
outer layer: blastocyst
will go on to form the trophectoderm layer, composed of trophoblast cells that are in charge of latching onto the uterine wall and will go on to form the surrounding fetal membranes
day 6-7 of preimplantation period
zona hatching
what is zona hatching
within 72 hours after reaching the uterine cavity, the blastocyst breaks out of the zona pellucisa
what does zona hatching allow
the trophoblast to come in direct contact with the uterine epithelium to begin the process of implantation
day 7-10 of preimplanation period
implantation
what happens during implantation
after the hatching the blastocyst will begin the process of implantation and attach itself to the uterine cavity
what is implantation
is the process by which the embryo attaches itself to the uterine wall
what are the three main stages of implantation
- apposition
- adhesion
- invasion
what is implantation: apposition
first connection between the blastocyst and the endometrium of the uterine wall is formed
weak contact- apposition
weak contact with the uterus occurs, wehre mircovilli on the surface of the trophoblast cells interdigitate with microprotruisons from the uterine epithelium (pinopodes)
pinopodes
cellular membrane protrusions that form on the surface of epithelial endometrial cells
appositions- pinopodes
are clear marker of endometrial receptivity as they are only present during the implantation window
apposition- inner cell mass
rotates inside the trophectodern in order to align with the endometrium
how does the embryo mange to attach in the correct position everytime
the occurrence of the rotation
implantation: adhesion when does it occur
around day 6 or 7 post fert
what is implantation: adhesion
a combination of inhibitory signals (mucins) and adhesive signals (cytokines and adhesion molecules) from the endometrial surface help the embryo avoid areas with poor chances of implantation and adhere to an appropriate spot in the endometrium
implanatation: invasion
- trophoblast cells begin to penetrate adn effectively invade the endometrium, anchoring the blastocyst in place
implanatation : invasion 9th or 10th day after conception
the blastocyst is completely embedded in the stromal tissue of the uterus, and the uterine epithelium has grown to cover the site of implanation
implanation: invasion
the trophoblast cells will then differentiate into an outer and inner layer each with specific functions
what does the differentation into outer and inner layer estbalish
the vascular link between the mother and fetus, ensuring access to nutrients for its growth
ectopic impanatation
ectopic pregnancy
- abnormal implantation of the blastocyst
- blastocyst implants at a number of sites outside the uterine body, with the most common site being within the fallopian tube
what are some spots of ectopic implantation
- ovary
- cervix
- fallopian tube
- abdominal cavity
window of implantation- role of preogestrone
progesterone secreted by the corpus luteum prepares the endometrium for implantation and is vital for a pregnancy to remain successful
successful implantation what does it depend on
synchronized interaction of a mature blastocyst and a hormonally primed uterus
window of implanation- endometrial receptivity
endometrium is typically not receptive to embyro implantation, excepting during WOI
when does the window occur
around days 6-10 post ovulation (day 20-24)
factors that influence endometrial receptivity
- acquires adhesion ligands
- loses inhibitory components
endometrial receptivity- acquires adhesion ligands
- under hormones factors such as adhesion molecules (integrins, selectins, cadherins and immunoglobulins) cytokines, growth factors, lipids
- mediate this early maternal-fetal interaction
what will cytokines do in the adhesion ligands factor
will attract the blastocyst to the optimal implanation spot
what do adhesion molecules fo
firmly attach the blastocyst to the endometrial pinopodes to ensure successful implantation
endometrial receptivity- loses inhibitory components
- near the WOI, there is a decrease in the synthesis of antiadhesive glycoprotein molecules which prevent receptor interactions between the blastocyst and endometrium, and thus act as barriers for invading embryo
loses inhibitory components- mucin-1 (MUC-1)
repels blastocyst and prevents adhesion to endometrial areas with poor chances of implantation
what will an receptive endometrium have
increased vascularization and enhanced secretary activity of the uterine glands
what is the decidulizatoin of the uterine lining
- when progesterone from the corpus luteum reaches the uterus and causes uterine glands to increase in size and stromal cells turn into large swollen cells containing extra quantities of glycogen, protein and lipids
what is the transformation of the uterine lining considered
a distinct tissue.
inner lining of uterus is called
decidua (throughout pregnancy) and is the tissue baby will interact with
what is histotrophic nutrition (from celld)
- until the embryo is able to connect to the maternal circulation, the nutrients provided by the decidua are the only source of nutrients it can receive
when can embryo get hemotrophic nutrition (from blood)
after around the 16th day of fertilization, the embryo will have access to the maternal blood
what are causes of pregnancy loss
- inadequate uterine receptivity
- problems with the embryo itself
recurrent implantation failure
is a cause of female infertility
- no gold standard marker that can accurately indicate or measure endometrial receptivity
