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What are the goals for the follicular phase?
Allow follicle to reach mature stage
Display estrus
What stages are part of the follicular phase?
Proestrus and estrus
What occurs during proestrus?
CL is killed,
Increased estrogen
Pushing follicle growth
What occurs during estrus?
Only period of receptivity to male
Peak estrogen
How often does the surge center “surge”?
Every 21 days (estrus)
What kind of feedback does estrogen have on the surge center?
When a dominant follicle is present, estrogen has positive feedback
When a dominant follicle is not present, estrogen has negative feedback
When does the tonic center start working?
From birth (never stops)
What is the main hormone in the tonic center?
Progesterone
Describe the activity level of the tonic center from birth to post-puberty onset.
Active at birth but slow release
Activity increases during puberty onset and during each follicular phase after puberty onset
What is Inhibin?
The follicle selection hormone
How does inhibin react with estrogen?
When inhibin is high, estrogen decreases
What type of nuclei are present in the tonic center?
Arcuate nucleus and Ventromedial nucleus
What does the tonic center do?
Stimulate basal LH needed for androgen synthesis in theca cells
Increases release of FSH needed for aromatization of androgen to estrogen in granulosa cells
What nuclei are present in the surge center?
Preoptic, suprachiasmatic, and anterior hypothalamic area nuclei
What are hormone levels like from the surge center during the luteal phase?
High P4 and low E2
Surge center is not active
Where are FSH and LH stored?
Gonadotrope cells
What are hormones like in the surge center during the follicular phase?
Low P4, high E2
What kind of feedback does the surge center receive during the follicular phase?
Positive feedback
What structure doesn’t have E2 receptors?
The hypothalamus
How much LH does the surge center release?
100-150 ng/mL
How much GnRH does the surge center release?
20-100+ pg/mL
Does follicle growth continue throughout the entire estrous cycle?
Yes
What dictates follicle growth?
Amount of FSH and LH in the blood
From smallest to largest what is the order of follicle size?
Cow, mare, sow
Sow, cow, mare
What stages of follicles have the most E2?
Large and pre-ovulatory follicles
What happens to follicles during the luteal phase?
Follicle growth still occurs, follicles just can’t reach dominance
What processes of follicle growth still occur during pregnancy?
Selection, growth, and recruitment
What occurs during the recruitment phase?
Small portion of primary follicles are selected and initiate growth
What are the 2 take-aways about how recruitment works?
Follicles will secrete AMH to inhibit follicles around them from being recruited
Oocyte orchestrates follicle progression
How many follicles typically start growing in cattle?
20
What occurs during the dominance phase?
Surviving follicle(s) continue to grow and increase E2 levels
Start to synthesize and secrete inhibin, decreasing FSH
What occurs during the selection phase?
LH starts to increase due to follicles secreting inhibin
FSH starts to decrease, inhibiting other follicles from growing
What is atresia?
Hormone controlled apoptosis
How does atresia work in monotocous species?
All but one follicle regresses
How does atresia work in polyocous species?
Utilizes E2/inhibin ratio to determine how many follicles survive
When does atresia occur?
Before a follicle can reach dominance
What environment is needed for a dominant follicle to form?
Low P4
What stage is inhibin released?
During selection
What type of receptors do dominant follicles have a lot of?
LH receptors
What stages can atresia occur?
During selection and dominance
Not during dominance pre-ovulatory
When is the first identifiable follicle wave in cattle?
During metestrus
What happens during mid-diestrus in cattle?
Second follicle wave is identifiable, but no dominant follicle will form
CL is present = high P4 = limited follicle growth → follicles regress and become atretic
What is occurring during the third follicle wave?
CL is regressing = P4 is decreasing
LH and FSH increase
Dominant follicle forms producing more E2
Mating and Ovulation
What is the ideal number of follicle waves?
3
During what periods of anestrus do follicle waves continue?
Prior to puberty
During pregnancy
During other periods of anestrus (lactational anestrus, illness caused, etc.)
What is the max number of oocytes ovulated for a cow?
136
Functions of FSH
Stimulate follicles to grow
Stimulates E2 production by granulosa cells
Functions of LH
Stimulates steroid production by theca interna cells
Initiates ovulation and lutenization
What cells help produce estradiol?
Theca and granulosa cells aromatize cholesterol to produce estradiol
Effect of estradiol in the hypothalamus?
Fires surge center
Effect of estradiol in the reproductive tract?
Tone myometrial layer; influence endometrium secretions (prep tract for sperm)
Effect of estradiol in the brain (behavior)?
Receptivity to male (estrus)
How is estradiol distributed throughout the body?
Diffuse through basement membrane to capillaries and bind to receptors
Lordosis “AKA”
Standing heat
What do leukocytes (immune cells) do in the reproductive tract?
Attack sperm
Protect from foreign material coming in with sperm
What does the oocyte have to pass through in order to ovulate?
Granulosa → basement membrane → theca interna and externa → intracellular connective tissue → tunica albuginea → peritoneum/surface epithelium
What is Hypermia?
Increased blood flow in ovary/follicle
What events are caused by LH surge?
Increased internal blood pressure in follicle (Hypermia) → breakdown of tissues forming follicle wall → contractions of ovarian smooth muscle
What does Hypermia cause?
Increase PGE2 and histamine (vasodilators)
Increase vasodilation, angiogenesis
Increase blood flow to ovary and pre-ovulatory follicle = antrum size increases (increased pressure)
What tissue holds the follicles and follicle wall together?
Collagenase
What does collagenase do?
Breaks down collagen in the follicle wall
What are the steps in wall breakdown?
Block enzyme in theca interna that converts P4 to T
Steroid synthesis stops at P4
Local P4 promotes synthesis of collagenase
Collagenase breaks down collagen in the follicle wall
Apex of follicle weakens and pushes out to form “stigma”
What happens when you block smooth muscle contraction with inhibitors?
Ovulation is blocked
What happens during wall contraction of the follicle?
Increase local PGF2 alpha production
Contraction of “myoid” components of ovary
What are lysosomes?
“Clean up crew”
Prepares follicle for lutenization
Rupture in granulosa
Enzymes in lysosomes disrupt connective tissue
What leads to ovulation?
Increased follicle pressure + weakened follicle wall
What is initiated by preovulatory LH surge?
Gap junction breakdown between granulosal cells and oocyte
Allows egg to continue meiotic journey so it’s mature enough for fertilization
What does OMI stand for?
Oocyte Maturation Inhibitor
What does MPF stand for?
Maturation Promoting Factor
What is Spontaneous ovulation?
Cyclic changes based on predictable hormonal event
Ex: cow, ewe, mare, sow
Male presence not needed to ovulate
What is induced ovulation?
“Reflex” ovulatory
Ovulatory process starts due to copulation (stimulation of vagina/cervix)
Ex: cat, rabbit, llama
What hormone change occurs during induced ovulation?
LH amplitude increases with increased mating
50% cats ovulate with one mating
Increased mating increase % ovulating
4 phases of oocyte maturation:
Prenatal mitotic divisions
Nuclear arrest in dictyotene of prophase 1 (“prolonged diplotene”)
Cytoplasmic growth
Resumption of meiosis at ovulation
When do mitotic divisions occur?
Occur prior to birth
What is the last mitotic division?
Oogonia → primary oocyte
What occurs during prophase 1?
Each chromosome duplicates = sister chromatids
Crossing over can occur
What is the purpose of Meiosis II?
Gametes are formed
Which process involves identical daughter cells and which mixes maternal and paternal genes around?
Mitosis produces identical daughter cells
Meiosis shuffles maternal and paternal chromosomes around = genetic variation
What are the methods in meiosis that result in genetic variation?
Crossing over
Independent assortment
What is the equation for number of combinations in independent assortment?
2 to the power of n
n = # of chromosomes
What is the chiasmata? When does it occur?
Site of crossing over; exchange of genetic material between non-sister chromatids
Occurs during synapsis of prophase I
What does crossing over produce?
Recombinant chromosomes
Chromosomes w/ DNA from maternal and paternal
What is formed in the primary oocyte?
The cytoplasm
What develops in the secondary oocyte?
Zona pellucida (grows to max size)
aids in single sperm fertilization
What is the process of oocyte growth?
Primordial oocyte → primary oocyte → secondary oocyte → tertiary small antral → tertiary preovulatory → mature ovulated oocyte
What is the interval from ovulation to luteolysis?
The luteal phase
Stages of the luteal phase?
Metestrus (increasing P4, CL developing)
Diestrus (High P4, full CL)
Major events of the luteal phase?
Formation of CL
Synthesis and release of P4
Luteolysis (when no pregnancy)
What do granulosa cells become during the luteal phase?
Granulosa cells → large luteal cells
How were large luteal cells formed? What do they do?
Granulosa cells increased during lutenization (hypertrophy)
Produce bulk of P4, oxytocin, and relaxin
What do theca cells become in the luteal phase?
Theca cells → small luteal cells (mostly liquid droplets)
How were small luteal cells formed? What do they do?
Theca cells increase in number (hyperplasia)
More receptive to LH
Fine tune P4 secretion
What structure is present during metestrus?
Corpus hemorrhagicum (CH)
temporary structure right after ovulation, similar to blood clot
What hormone has a minimum required amount to maintain a pregnancy but not a maximum amount?
P4
What is required for P4 synthesis?
Cholesterol substrate
Tonic LH stimulation
What is the role of LH stimulation during P4 synthesis?
LH increases amount of cholesterol moving into mitochondria to make P4
What happens to the CL during luteolysis?
Functionally killed
Tissue is still present
What kind of feedback does P4 have on the tonic center? What is that effect?
Has negative feedback on tonic center = negative feedback on GnRH/Pituitary
What tissues are targeted by P4? What are some of the effects?
Target: Alveolus of mammary gland
Effect (+ feedback): Puberty onset, prepare mammary glands for milk (not milk production)
Target: Uterine tissue
Effect (+ feedback): Increase uterine duct secretion
Effect (- feedback): Relax myometrial layer = better environment for embryo/gestation
Target: Hypothalamus
Effect: Negatively regulate GnRH from pituitary gland
What hormones from where signals for luteolysis?
PGF2 alpha from the uterus
Oxytocin from the CL