Chapter 4 Flashcards

(55 cards)

1
Q

Presence of SRY on Y chromosome

A

***the prescence of SRY (gene) on the Y chromosome leads to SOX-9 (protein)

  • SOX-9 differentiates the tissue to form testes
    ○ Testes produce testosterone
    ○ Testosterone gets access to the brain and creates sex differences
    • Active process for ovaries but don’t need to know hormones (however having ovaries is not a default process)
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2
Q

Organization vs. Activation of the Brain

A

***steroid hormones are important for organizing the brain and adult sexual behavior

***later they activate the brain after puberty

Organization vs. activation:
- Increase in testosterone goes into the brain and organizes the brain differently
- When hormones are present in adults, it will act on those systems to regulate the behavior

  • A massive surge in hormones changes the brain’s structure (organization)
    ○ Then that person goes through puberty and the activation is the body acting on those hormones
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3
Q

Organizational Effects

A

early in development (prenatal and parinatal)
- steroid hormones permanently order the structure and other tissues that lead to development of other structures

activation:
- later in life, when that person goes through puberty, tesosterone acts on those structures to influence behaviors
- ex: during puberty, sex hormones can activate sexual behaviors

**early hormone structure (organization) sets the stage for later hormone actions (activation)

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4
Q

Male and Female Rat Sexual Behavior

A

major differences between male and female rats

males sexual behavior = numbering the amount of times they mount the female

female = arching the back when the male mounts them

**behavior in rats is organize during development

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5
Q

XX and XY rat behavior

A

XX:
- Low levels of estrogen after a few days after birth
- If you gave a female high levels of estrogen and progesterone you would get high levels of female sex behavior
- Females will exhibit some low levels of tesosterone behavior (male)

XY:
- Present of SRY and formation of testes
- The testes secretes high levels of tesosterone on first day of life
- The brain is aromatized into estradiol
○ That causes organization of male cuircutry
○ *estrogen masculinizes the male rat brain during their first day of life

  • High levels of tesosterone = shows high levels of male sexual behavior
  • Low levels of tesosterone = low levels of male sexual behavior
  • If you give males estrogen and progesterone, you will get a male with low levels of female sexual behavior

***if an animal is given testosterone early in life, they are more likely to show male sexual behavior and low levels of female sexual behavior (vise versa for females)

**Main differences:
- testes release tesosterone first day in life (the brain then gets aromatized to estrogen) and brain is masculinized
**
The majority of behavioral phenotypes or physiological phenotypes that are skewed toward the male is because of estrogen receptors in the brain

  • Progesterone receptors have an unclear role

***The exposure to hormones are very brief (within first 24 hours of life) can create a lasting effect on behavior that they show in adulthood

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6
Q

Video Notes - Rat Sex Behavior

A

**they compared areas of male and female brains

***the hypothalamus area in males is 5x bigger than the area of the hypothalamus in females
○ Rats and humans start out with potential to develop into female and male sex behaviors
○ The presence of testosterone during development changes the brains
○ Giving females an injection of testosterone gives the females, male sex behaviors
○ Ex: the female that is injected with testosterone will hump the other female

○ Ex: the female injected with testosterone will hump the male rat that was castrated that acts with female sexual behavior

  • If you expose male to androgens (tesosterone) it will behave like a male with sexual behavior
  • *just takes one injection of tesosterone after birth to drive sexual behavior
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7
Q

Ex of Giving Androgens

A

if you give androgens, it will organize and then it will cause male sexual behaviors

organization: androgens exposed after birth

as animal ages, testes secrete very low levels of testosterone

animal goes thru puberty
activation: once animal goes thru puberty, the animal starts showing male sexual behaviors

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8
Q

Brain can be Maculnizied or Feminized depending on what it’s Exposed to

A
  • Alpha-fetoprotein (comes from liver and mom) is present in the babies when they’re born and then it absorbs all of the estrogen
    ○ It protects the brain from estrogen

If testes are present, they release tesosterone
○ Testosterone isn’t bound by alpha-fetoprotein so the testosterone goes to the brain, then the brain is aromatized by estradiol, which causes masculinization in brain

newborn:
- high levels alpha-fetoprotein and then it drops
- Protects brain of expoisure of estrogen but it doesn’t block the androgen from getting to the brain

**female brain is shaped by low levels of estrogen (first week)
***second week of life is shaped by estrodial (still much lower levels)

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9
Q

Anatomic Sex Differences: Volume of tissue

A

*all of the antomical differences are driven by tesosterone and estradiol

volume = single injection of testosterone will masculinize the brain and make it bigger

differences in SDN: third ventircle
- the large nucleus is the male brain (the SDN is bigger in male brain than the female brain)

***This is because of androgen exposure (and estrogen exposure)
- Birth- males : they have tesosterone surge – causes larger SDN in males
Birth - females: low levels of testosterone, which causes smaller SDN in females

***giving estrogen causes a masculnized size of the nucleus in SDN

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10
Q

Androgen Exposure - Volume for Brains

A

**androgen exposure on the first few days of life
Males: have testosterone surge
- in adulthood, they have a large SDN
female: not given testosterone to small SDN

If given testosterone injection to female:
- this gives them a msculinized size of the SDN
**if you give the female the injection after the sensitive period, then they won’t have a masculinized size of SDN later in life

***need androgen exposure during sensitive period to masculinize the brain
- If you’re stressed during the sensitive period, more lasting effects

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11
Q

Anatomic Sex Differences: Cell Death - SDN

A

*all of the antomical differences are driven by tesosterone and estradiol

Cell death: if you have sex differences in volume, it could be due to cell death

*Males have larger volume of SDN because androgens alter cell death
- Tesosteroen on first day of life saves cells in the SDN
- Males have larger SDN and females get smaller one
- During development, they have the same SDN size
○ But the exposure to androgens, stops the cell death in the SDN which keep it big

  • ***estrogen and androgens can’t change the SDN size because the cells in the feminized SDN are already dead

***The estrogen blocks apoptosis
- These cells would have died in the SDN, unless they had androgen exposure which would have blocked cell death from happening

Fewer cells undergo apoptosis If they were given estrogen in this brain region

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11
Q

Cell Death in the AVPV

A

AVPV = other brain area
- Involved in regulating cycles in female rats
- Testosterone kills cells in this area (*testosterone doesn’t save cells everywhere)
- Lack of tesosterone causes larger AVPV

if you stain brain w estrogen receptors:
- The female has a lot more estrogen receptors than the males do
-***Females have larger AVPV then males

Androgen exposure or estrogen can decrease cell death in the preoptic death, but that same hormone in a nearby brain area can kill off cells

  • Estrogen protects in one are and kills off in another cell
    ***depending on location of brain, estrogen can be protective or kill off cells
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12
Q

Anatomic Sex Differences: Connectivity

A

*all of the antomical differences are driven by tesosterone and estradiol

connectivity:
- Vasopressin cells project thru a lot of brain regions
- They also project deep into the brain (amygdala and BST) and the pituitary gland

**high levels of vassopressin in the bed nucleus of the stria terminalis in males

  • More vasopresin cells in the bed nucleus, there will be more fibers and connections going to those cells
  • ***BST has more vasopressin cells in the male, they have more fibers which control behaviors like aggression

*vasopressin cells (more in the male due to androgen exposure) so more fibers going to the lateral septum which is related to aggression
**in females, fewer vasopressin cells so fewer fibers going to the lateral septum

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13
Q

Anatomic Sex Differences: Cell Morphology

A

cell morphology: how cells look and are different

Arcuate Nucleus:
○ There are spine were the synapsis can occur
○ Females have much more neural spines (driven by androgen and estrogen)

○ **if you castrate the male on the first day of life, that leads to increased spine formation (density)
— So we know that androgens are suppressing spine formation
○ **if you expose females to androgens, then they won’t have as many spines

opposite for glia:
- the intact male will have more stellate class 4
- females will have more of class 1
- if you give the female estrogen, it pushes the female toward the male phenotype
***females have less complicated glia structure (they have more spines, but their glia are less differentiated) — opposite for males

Glia:
- Glia changes synapses in neurons
- If you have stellate at glia, that inhibits synapse formation (which is why in males, fewer synapses)
- In females, their glia are less differentiated which allows for more synapses to occur

**neurons and glia move together/opposite in communicating (they’re related)

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14
Q

Anatomic Sex Differences: Expression of Protein

A
  • Major difference during development, doing immunocytochemistry you can tell if it’s a male or female rat by looking at density of preoptic
  • Males on first day of life have huge increase of progestorone recpetors than females
    ○ Progesterone receptors are made because of estrogen
    ○ Males have tesosterone that is aromatized in estrogen which is why they have a lot more progesterone receptors
  • If you castrate on first day of life, the progesterone receptors go away
    **sex differences are completely based on hormones

*if females are given estrogen or androgens cause progesterone receptors to form

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15
Q

Anatomic Sex Differences: Migration

A

Hormones can determine a little bit where cells are moving

*the cells start moving faster after the brain is given estrogen

Estrogen can increase movement of cells within the brain
- ***female brain can move faster than males under baseline, because sometimes the female produces estrogen to compensate

  • If you give estrodial, estrogen increases movement of cells within the brain
    – In males, adding estradiol causes the cells to move
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16
Q

Anatomic Sex Differences: Neurogenesis

A

neurogenesis = cell birth
***estrogen increases in the hippocampus

Estrogen can kill cells but also cause them to divide (neurogenesis)

  • Ex: using immunocytochemistry to detect chemical (BrdU)
    ○ Similar in structure to thymidine – important because when DNA divides, if BrdU is there, it adds it into the DNA
    ○ The BrdU is incorporated into the DNA of the dividing cells

If estrogen was causing cell division to happen, Brdu would be in that cell

**A lot of neurogenesis occurs in the hippocampus
- In the hippocampus, the number of dividing cells (with Brdu) males have more neurogenesis occuring then females
- If you give females estrogen, then females and males have the same pattern
- If you give males estrogen, they already have estrogen, so nothing happens
***estrogen causes neurogenesis

environment can change neurogenesis:
-Exercise can increase BrdU expression – animals that run more will have an increase in neurogenesis
- Exercise might be protective of not getting alzheimers because there’s more blood flow here and more neurogenesis

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17
Q

Sex differences in cell death and cell birth/Summary

A

**sex differences in cell death, where estrogen can protect against cell death or cause cell death to happen (depends on where the cell is)
**
if you’re in the preoptic area, estrogen is protective

summary:
- males have bigger SDN and smaller AVPV
- males have more vassopressin cells
- males have more progesterone receptors
- estrogen can increase movement of cells
- if you inject BrDU in estrogen, you can increase the cells in the hippocampus

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18
Q

Development of Testosterone

A

testsoterone gets released from the testes

  • Then aromatized into estradiol
  • Or it can be reduced into dihydroestesotserone
  • Estrodiol causes reorganization in the developing brain
    ○ Early surge in hormones organizes brain
    ○ This causes masculinization (increased of male typical behavior traits) and reduce feminization (lower levels of female sex behavior)
    • *you can manipulate the hormones (can interfere with masculinization, feminization, or both

*brain masculinization and defeminization

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19
Q

Epigenetics

A

our environment shapes our epigenome

epigenetic modifications are stable and heritable changes (across cell division) in gene expression and cellular function (doesn’t change DNA sequence though)

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20
Q

Genetics

A
  • Your body has the same genome
  • Egg fertilized by sperm, and then those cells divide
  • At one point, then you get tissue differentiation
  • Ex: skin cells, thyroid cell etc, all have the same DNA but they look different and function differently
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21
Q

DNA Size

A

if you took DNA out of cell and stretched it a lot, it would be very long
- now tiny when packed back in

  • Can’t make DNA small randomly – DNA would break and get damaged
  • Need to organize the DNA
  • Also don’t want all genes to be regulated all at one
  • ***need mechanism that can turn genes off sometimes and turn other genes on sometimes
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22
Q

Histones

A

Cell now organizes DNA in a tight, controlled way

  • DNA gets wraped around proteins (histones) – way to wind up DNA into compact structures so you can regulate them

○ Now you have tiny piece of DNA inside cell – now it’s hard to transcribe and turn on genes

23
Q

Opening DNA

A
  • When you look at compact DNA, to turn the gene on you have to open it
    ○ Ex: steriod receptors recruits coactivators
  • Can’t get all of the proteins in compact DNA, but if you unwind it a little, now the gene can be read
    ○ When you’re done, you rewind it up

epigenetics = understanding opening and closing of DNA

24
DNA Methylation
DNA methylation: ○ Transfer of methyl group (take cytosine and add methy group) - § Adding the methyl group changes someone and their lifespan ○ Whatever happens in your lifespan, if they do this methylation, it can be passed onto generations ○ When you have stressful experiences, sometimes they're so bad they last through the lifespan --- can they be passed on to offspring?
25
Methyl Mark and Process
*know what is methylation (adding methyl group to cytosine and it's the backbone of DNA) process: - DNA with gene transciption turns gene on - if you add methylation on DNA, the gene transciption can be blocked (gene off) - methylation can also reduce gene transcription (gene dimmed but not off)
26
Mixer for genes
HELP can alter how teh gene responds to the environment ultimately, epegentic markings will be mixers (change the gene expression but also can dim or intensify the gene)
27
Summary of Methylation
when gene is switched on = unmethylated state - active chromatin (unmethylated cytosines) - when you add methyl group (DNA closes up) - silent chromatin - methylated cytosines DNA = negative ○ Histone = positive ○ When you move the charge it loosens up - When you add the charge, the DNA closes back up
28
Parental Care
maternal care can alter epigenome paper: studied parental care - They noticed that if a mom was attentive and licking/grooming their animal, that animal will be less stressed later in life - The moms that were more neglectful, those animal grew up and showed more stress and anxious behavior
29
Maternal Care
- There's not that much a rat can do to exhibit maternal care except lick, feed, groom - So you measure the time of the rat enagaging in that behavior - They thought there was an epigenetic event (during first week of life) that the mom was doing that was changing the genes for anxiety - So when the animal grows up, it can be altered
30
Measuring Care
classified maternal care: ○ Measured the time on the nest of the mom grooming, licking, etc. (during first week of life) ○ They get the curve (those that are 2 SD on the right and left are the good and then bad moms) groups: Those raised by the higher tail end of the graph were more relaxed and had better coping behavior *a pup raised by anxious, low nurturing mom, becomes anxious adult **pup raised by relaxed, high nurturing mom becomes relaxed adult
31
Stress Pathway
Pathway of Stress: - CRH cells in hypothalamus release CRH into pitutiary - Those cells release ACTH which causes release of cortisol - That goes back into the hippocampus A lot of our emotions (fear, hurt) are processed by the amygdala ○ That activates the hypothalamus ○ That releases cortisol and then that goes up to hippocampus - The hippocampus reads the cort. says we have to dampen the stress response
32
Glucocorticoid Receptor - Stress Response
Secretes ACTH, cortisol comes out and goes into the hippocampus to dampen it study: maternal care can change glucocorticoid receptor expression and stress response *** - The pups from good maternal care have high gluc. Recpetors (respond to the increase of - Hippocampus is involved in stress response -- has gluc. Receptors and then responds and tells cells how they should act
33
Methylation and Glucocorticoids
looked at methylation on gluc. gene If you measure amt. of methylation prior to birth on gluc. Receptor, it's low ○ Once the animal is born, that gene is highly methylated ○ At diferent times, animals in a low maternal care environment, they remained high in methylation on that gene ○ Those in the hiugh maternal env. Had reduced methylation on that gene Rats go thru pubtery arbound p40 ○ The change in methylation that happens from the high/low licking environment, stays in their adult life *if you have lower methylation, you get a higher output (protein goes up) *that higher GR = more adaptive *low GR = less adaptive
34
Rat Immobolization Study
made enclosure for rat to not be able to move - rats don't like being in the light if you put the rat in a tube, they want to stimulate a burrow collapse where they can't move ○ Stress we don't have control over is worse than stress we do have control over ○ If you measure cortisol before to being enclosed, it's low ○ You put the animal in tube, within 15 minutes, a cortisol response happens (it goes up and then goes down within an hour) ○ **classic way to measure stress response
35
Stress Levels in Rat Licking
*low GR in hippocampus, lower feedback, cort is not reduced in response to stress *if you do this with animals from mom with high licking vs low licking -- there's differences *cort goes up *those from the low licking group, their cortisol goes up higher and their ACTH goes up - It stays higher for low licking group - For high licking rats, their stress goes up, but it does go back down ***if you have lower gluc. Recpetors in the brain, you won't have as good of a stress response when you get stressed
36
Summary of variations in maternal care altering glucocorticoid receptors
- The variations in maternal care can alter the gluc. Receptors, cause methylation, and alter stress response - Less methylation on GR gene, leads to high expression of GR and low anxiety - Opposite for rats with low licking (low maternal care) - High maternal care: ○ "licking" away the methyl marks ○ Increased GR in hippocampus, better stress response Low licking: ○ Mark stays ○ Animal will be anxious later in life
37
Glucocorticoid Gene
If you methyl the area of the promoter region, it blocks the transcription factor from binding to the gene by closing it (physical process) --- closes the DNA so it can’t be read or transcribed - Low methylation, less transcription factor binding, less gene expression, high anxiety *if you have higher GR, you have low corticosterone levels and high licking or grooming (opposite for lower GR)
38
Weight in Babies
weight is important in babies - if you hold babies, they will gain weight faster ○ By measuring change in weight is important (released faster from nicu) § Has health implications § Those with increased contact perform better academically § Those that didn't have contact do worse and have lasting impacts
39
Sex Differences in Maternal Care and estrogen receptors
**mom licks male rats a little more than female rats - She licks the anal/genital region because those animals have hard time to eliminate waste and the sensory touch helps them - Males have testes (secrete androgens) that changes the acidity of the urine ○ Something that the androgens is doing that changes the urine - Estrogen receptors in brain: ○ Females have more than males in some areas ○ More estrogen receptors in RNA or protein ○ Sex difference in estrogen receptor and protein
40
Paintbrush Stroking Rats
- Tested by holding rat first few days of life, and stroked anal/genital region ○ The paintbrush stroking mimicked the licking ○ The controls were just held (not stroked) - Androgen receptors -- get masculinized by the licking ***maternal licking increases methylation and decreases estrogen receptor expression
41
Females who get extra licking
- Females that receive the extra licking, had closer to female like control levels ○ The licking and grooming stimulated pattern, made higher ○ In simulation: painting on methylation marks § A stimulus can lead to different directions of promoter genes - Maternal care: mom licks off methylation (doesn't lick off all of methyl marks)
41
SRY Gene in Licking Rats
- SRY gene increases SOX-9, makes testes which secretes tesosterone - That increases the urine diff. which causes the mom to lick them more -- The SRY gene can manipulate the mom to come over and change how that rat is being raised (being licked more)
42
Krol Study: oxytocin research
○ Oxytocin receptor research ○ She found that babies that are near attentive caregivers show reduction of epigenetic modification on the oxytocin recpetor gene (lowered methylation) ○ Oxytocin is involved in bonding § Oxytocin went down when cared for more ○ The reduction lasted at least the first 18 months of the baby's life ○ ***how you care for a baby can have a big effect later on in life ○ Touch is very poweful for a baby
43
Oxytocin Levels in Parent
- Increased maternal oxytocin levels were when the mom was more affectionate to the baby - parents with higher oxytocin levels showed more sychrony and responsiveness to their infant interaction Paternal oxytocin levels: - Increased oxytocin levels when there was more physical contact *differences in how parents interact with their baby
44
BDNF from binge drinking
BDNF is important for neurons to survive and grow ***it can be a neurotransmitter modulator and is important for neural plasticity (needed for learning and memory) they looked at BDNF consequences of binge drinking - BDNF is a good protein - if you sleep, increases BDNF - *cortisol acts against BDNF (low BDNF when stressed)
45
Consequences of Binge Drinking
study found that found that adolescent drinking can epigenetically alter BDNF **teen drinking lowers BDNF **they found another gene increases from bindge drinking (this is an anti-sense (BDNF anti-sense) -- this lowers BDNF *ppl older than 21 -- drinking doesn't really affect BDNF as much
46
Antisense Molecules
Our bodies can produce anti-sense molecules - Little RNA molecules that don't code - They might target an RNA and form a hybrid -- cells hate double-stranded RNA so it has cells go and break up the RNA hybrid and then gets degraded - So if you have an increase in anti-sense BDNF, it will bind to BDNF and then make a hybrid, the cells will degrade it and then you won't make BDNF
47
Rat Study on Binge drinking
- Exposed adolescent female and male rats to alcohol - After they were sober, they were mated and then they looked at the offspring *they raised the offspring and then looked at their social interactions results: ***they found that those parents that engaged in alcohol abuse prior to conception, they weighed less - The rats with parents exposed to alcohol, the offspring played less - ***effect that impacted the gametes that when they fertilized, there was an impact of binge drinking prior to conception **in males, binge drinking effects methylation on sperm
48
Diet
Methyl donors - mythlation comes from methionine, folate, vitamin D, etc… - Our diet is responsible for the methylation of DNA foods high in folate: beans, rice, spinach - folate allow for the enzymes to drop methylation onto our DNA
49
BPA (Plastic)
BPA is in a lot of things (waterbottles, toys) - when you heat plastic, BPA gets into it BPA = endocrine disrupter - binds to estrogen recpetors but then causes them to be a diff. shape - it twists differently - Interacts with different coactivators and then works differently ***endocrine disruptor
50
Agouti Gene
all mammals have agouti gene = makes brown rat because agouti gene has been methylated if coat color is brown = gene has been methylated Animals exposeed to BPA, results in demethylation of Agouti gene ○ Removal of methylation, animal becomes yellow, risk to obesity and cancer - The coat changes (you can see when it's methylated or not) study: moms fed low or high BPA - if mom gets fed high BPA, then offpspring looks more yellow and is heavier if you make diet that increases methylation: ***they found that the high methyl diet blocked the cosequences of BPA (***if you consume BPA but also get high methyl diet (from folate), then the effects of the high BPA levels aren't as bad)
51
Mice Study - BPA Summary
when mom's were fed BDP, their babies were more likley to be yellow and obese **when the moms were fed BPA and methyl-rich foods, the offpsring were more likely to be brown and healthy ***the maternal supplementation counteracted against the neagtive effects of BPA exposure
52
Identical Twin Study
looked at identitical twins and their methylation profile 3 year olds: very similar profiles older twins: very different **when you have twins, even with the same DNA, because of epigenetics, they can have different diseases later on ex: if one has more methylation in their diet, might not get alzheimers **as they get older, their DNA sequence stays the same, but their epigenetic tags can change depending on their life
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Epigenetic Patterns can be Reversible
vassopressin study: - if you castrate, remove tesosterone, vasopresin goes away - If you give tesosterone, vasopresin goes back up - Intact animal, low promoter methylation (genes open) ***Hormones are reversing the methylation