ESTROUS AND
MENSTRUAL CYCLES
ANSC 631
SPRING 2014
What are you expected to learn?
What is an estrous cycle?
How does it differ from a menstrual cycle?
What organs are involved?
What hormones are needed?
How/where estrogen and progesterone are synthesized?
What endometrial changes occur during the estrous and
menstrual cycles?
Menstruation: why and how
What happens in a fertile cycle
Outline for Presentations
• Estrous and Menstrual Cycles
• Gonadotropin Regulation of Follicular Recruitment and Development
• Follicular Steroidogenesis
• Growth Factors and Follicular Development
• Ovulation
• Corpus Luteum Formation, Function and Angiogenesis
• Luteal Peptides, Cytokines and Growth Factors
• Prolactin and Ovarian Function
• Luteolysis.
Reproductive cycles: Animals vs Women
Animals
Estrous cycle The physiological
events between successive
periods of sexual receptivity
&/or ovulation – Day 0 is day of
onset of estrus
Anestrus Without cyclicity -
caused by pregnancy, season,
lactation, stress (under-
nutrition, environment)
Women
Menstrual cycle The
physiological events between
successive menstruations
(~28d) – Day 1 in day of onset
of menses
Amenhorrea lack of menstruation
– caused by pregnancy,
lactation, stress, pathologies
Reproductive cyclicity provides females with repeated
opportunities to become pregnant
What was normal in ancient times?
If no conception in a cycle, another cycle begins to provide a new
opportunity to establish pregnancy
Estrus = heat = period of sexual receptivity
–Estrus is a noun. (estrus)
–Estrous is an adjective (estrous)
Cyclicity - categorized according to frequency of
occurrence throughout the year
Polyestrus
cattle, swine, rodents
Seasonally polyestrus
sheep, goat, mare,
deer
Monoestrus
dogs, foxes
Senger 2003
Classifications of Estrus
Physiological Estrus – Follicle Growth, Estrous behavior,
LH surge and ovulation with outcome being synchronized
mating and ovulation to maximize chances for fertilization of
oocytes and establishment of pregnancy.
Characteristics
- Increase in estrogens from mature Graffian Follicles
- Increase in GnRH synthesis by peptidergic neurons in
hypothalamus
- Increase in GnRH pulse frequency
- Increase in GnRH Receptors on Gonadotrophs in Anterior
Pituitary
- LH surge and Ovulation
Psychological Estrus – Estrous behavior without ovulation
1. Estrogens – effects in area of hypothalamus (work with
cats identified nuclei for estrous behavior without ovulation)
Pre-optic area - +++
Arcuate Nucleus - ++
Mammalary Body - +
2. GnRH – Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-
GlyNH2 Receptor Binding Lordosis
3. Oxytocin – Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2
a. Smooth muscle contractions – sperm transport,
lactation, parturition
b. Bonding
mother and offspring
sexual partners
Yen 2004; Reprod Endocrinol 3-73
Hypothalamic Divisions
Characteristics of Psychological Estrus
Increased activity: walking, vocalization, mounting,
accept male for mounting/mating
Example: Post-partum Estrus in Sows
a. Estrous Behavior 2 to 3 days post-partum
b. No Ovulation
c. Cause: Likely prepartum estrogens
Post-Partum Estrus Sow
- 2-3 days – Psychological Esrus Only
- Post-weaning estrus – 72 to 96 h is fertile
Mare
7-10 days post-partum – fertile
Beef Cows
60-80 days postpartum due to suckling intensity
Dairy Cows
2X Day Milking – 14 Days Postpartum is short cycle usually
21-25 Days Postpartum for normal cycles
Ewes – Normally Lamb During Anestrus Season
Mouse and Rat – Day 1 postpartum – fertile and followed by delayed
implantation
Humans – Variable due to suckling intensity and nutrition
DELAYED IMPLANTATION
• Embryonic diapause, temporary suspension of
blastocyst development in mammals due to
suppression of cell proliferation.
• Obligate diapause occurs in every gestation of
some species, e.g., season to time birth with
favorable time of year for nutrients
• Facultative diapause is associated with
metabolic stress, usually lactation, to prevent
concident lactation and pregnancy.
3) Delayed implantation (Chiroptera, Carnivora, Xenarthra, Cetartiodactyla)
Zona Pellucida
Mechanisms for Optimizing Timing of Birth
Obligate
Ursus americanus
Facultative
Many Rodents
4) Embryonic diapause (Macropodids)
Mechanisms for Optimizing Timing of Birth
DELAYED IMPLANTATION IN WALLABY
JANUARY BREED AND NEW YOUNG TO TEAT TO SUCKLE AND INDUCE
FACULTATIVE DELAYED IMPLANTATION (LACTATION/SUCKLING
INDUCED)
CORPUS LUTEUM PRODUCING LITTLE PROGESTERONE
TREATMENT WITH BROMOCRYPTINE TO DECREASE PROLACTIN AND
DELAYED IMPLANTATION CAN BE INTERRUPTED
JUNE-JULY OBLIGATE DELAY DUE TO SEASON/PHOTOPERIOD
DECEMBER POUCH YOUNG OUT + ABOUT 28 DAYS AND FEMALE RETURNS
TO ESTRUS
JANUARY BREED AND REPRODUCTIVE CYCLE BEGINS AGAIN
Figure 1 Strategies for photoperiodic modulation of diapause employ melatonin and prolactin for contrasting purposes.
Lopes F L et al. Reproduction 2004;128:669-678
© 2004 Society for Reproduction and Fertility
Figure 2 Summary of uterine influences that could be acting on the dormant embryo in the rodent model to terminate the mitotic arrest of diapause.
Lopes F L et al. Reproduction 2004;128:669-678 © 2004 Society for Reproduction and Fertility
LIF – Leukemia Inhbiting Factor
ErbB – EGF Receptor
EGF – Epidermal Growth Factor
Anandamide -
Types of Ovulation
A. Spontaneous Ovulators – Women, Domestic Animals – Endogenous
hormonal changes adequate to stimulate ovulatory surge of LH and ovulation.
B. Spontaneous Ovulator with Induced CL Formation – Rodents – Spontaneous
Ovulation; Mating Induced CL Formation
C. Induced Ovulator – Mating or stimulation of vaginal-cervical area results in
noradrenergic stimulation of hypothalamic GnRH centers to cause release of ovulatory
surge of LH - rabbit, mink, cats. In rabbits, ovulation about 10 h post-mating or
stimulation of vaginal-cervical area. In domestic cats, multiple matings usually
required for full ovulatory response.
D. Seasonal Ovulators
1. Monestrus – bears, dogs (most big breeds) ovulate once per year
2. Long-Day Breeders – horse is seasonally polyestrus species
3. Short-Day Breeders – ewe is seasonally polyestrus species
Hormones of the Estrous and Menstrual Cycles
A. Luteotropic Hormones – LH, hCG, prolactin that act directly on CL to
stimulate progesterone (P4) secretion.
B. Luteolyic Hormone – Prostaglandin F2-alpha (PGF) that acts on CL to
cause cessation of secretion of progesterone and physical destruction of luteal cells.
Luteolytic PGF is from uterine epithelia in subprimate mammals and from intra-
ovarian sources in most primates, so menstrual cycle in uterine independent while
estrous cycles are usually uterine dependent.
C. Antiluteolytic Hormones – Interferon tau (ruminants), estradiol and
prolactin (pigs), prolactin and lactogenic hormones (mice)
D. Luteal Protective – Prostaglandin E2 may antagoinize luteolytic effects of
PGF2-alpha
Stages of the Estrous Cycle
A. Estrus: High Estrogens from Mature Graffian Follicles
and LH Surge
1. Follicle Maturation
2. Oocyte Maturation
3. Estrous Behaviour (Psychological Estrus) and
Mating
4. Estrogen-Induced Ovulatory Surge of LH
(Physiological Estrus)
5. Ovulation
6. Initial Luteinization of Granulosa and Theca Cells
7. Decreased Vaginal and Rectal Temperatures
0.25 to 0.75 degrees C
Increased blood flow to perineum area
Monitor time of ovulation
8. Increase in cervical mucus
Unique crystallization patter of mucus – ferning pattern
9. pH of vagina increases to 6.8 from 7.1 to 7.4
10. Increased antimicrobial actions
Increase in Lysozyme – bacteriacidal
Increase in Lactoferrin – bacteriostatic
11. Pheromones for attracting male
a. Cow – acetaldehyde (Bill Klemm, TAMU)
b. Rhesus Monkey
Copulin – short-chain fatty acids: acetic acid,
proprionic acid, isobutyric acid, butyric acid, and isovaleric acid
c. Microflora of vagina produce pheromones
12. Swelling of sexual skin - Vulva
Metestrus: Ovulation and Corpus
Hemmorhagicum (Corpora
Hemmorhagica)
1. Circulating Estrogens and
Progesterone are LOW
2. Uterine cells expressing
receptors for progesterone (PGR),
estradiol (ESR1) and Oxytocin (OXTR)
Diestrus: Corpus Luteum (Corpora Lutea) and Progesterone
1. Circulating Progesterone is HIGH
2. Large luteal cells of CL synthesize and store, depending on
species, oxytocin-neurophysin (ruminants) and relaxin (pig)
In sheep and cow: OXY production:
Days 0-3 transcription (maybe in response to LH surge
Days 4-7 translation of OXT-Neurophysin mRNA
Days 8-14 storage of OXY-Neurophysin
Days15-17 pulsatile release of OXT and Neurophysin
3. Steroid Receptors in Uterine Endometrium
Uterine epithelia and stromal cells: NO OXTR
Uterine epithelia lose ESR1
Uterine epithelia lose PGR after Days 11 to 12
Uterine stromal cells express PGR and low or no ESR1
4. Preparation of the Uterus for Pregnancy – Uterine luminal
and glandular epithelial cells begin to express proteins important to
development of embryo/conceptus (conceptus is embryo and its
associated membranes)
Late Diestrus – Corpus Luteum Regression
1. Steroid Receptors in Uterine Endometrium
Uterine Epithelia have increasing expression of ESR1
and then OXTR
2. Increase in estrogens from developing follicles stimulate
more ESR1 and OXTR in uterine epithelia
3. Oxytocin released from CL and/or Posterior
Pituitary in Ruminants and Posterior Pituitary and/or Uterus in
sows and mares
4. Oxytocin-induced luteolytic pulses of PGF2a
5. Corpus Luteum Regression
Proestrus – Corpus Albicans (Corpora
Albicantia) and Mature Graffian Follicles
1. Circulating Estradiol Increasing
2. Circulating Progesterone Decreasing
to basal levels
3. GnRH Pulse Frequency increasing
from 1 pulse/2 to 4 h to approximately hourly
pulses
Fig. 7-3
Regulation of Corpus Luteum Function
Species Luteotrophic Complex
Human LH
Sheep LH & GH
Pig Estradiol
Pseudopreg.
Rabbit Estradiol, LH
Pseudopreg.
Rat/Mouse Estradiol, Prolactin & LH
Organs involved in female reproductive
cycle
hypothalamus
anterior pituitary
Oviduct
endometrium
ovary corpus luteum
uterus
Ovarian Cycles: Uterine-Dependent
and Uterine-Independent
Major hormones regulating the female
reproductive cycle
Hormone
gonadotropin-releasing
hormone - GnRH
luteinizing hormone - LH
follicle stimulating
hormone - FSH
estradiol 17 (E2)
Progesterone (P4)
Site of production
hypothalamus
anterior pituitary
(gonadotrophs)
ovarian follicle
corpus luteum
After ovulation, cells of dominant follicle give rise to the CL
The female hypothalamo-pituitary ovarian
axis
GnRH
Inhibin
Activin
Follistatin
ovary
Pituitary
Gonadotrophins
(LH, FSH)
Steroids
Hypothalamus
Feedback hormones
Steroids
/ Uterus
Estrous cycles consist of two major
phases
Follicular phase
Ovarian FOLLICLES -
dominant structures in the
ovary
ESTROGEN is the
dominant hormone
Luteal phase
CORPORA LUTEA –
dominant ovarian
structures
PROGESTERONE is the
dominant hormone
Follicles grow Corpus luteum develops / regresses
The estrous cycle has 4 stages
Proestrus – formation of ovulatory follicles + E2 secretion
Estrus – sexual receptivity + peak E2 secretion + ovulation
Metestrus – CL formation + early P4 secretion
Diestrus – substantial secretion of P4
Phases / stages of the estrous cycle Most animals - short follicular phase
Senger 2003
GnRH, FSH and LH
• Pulsatile secretion
• Changing frequency
& amplitude
Hormone cyclicity in menstrual cycle
Positive feedback of peak
E2 induces preovulatory
LH surge
In Women – Menstrual cycle
Differs from estrous cycle
no defined period of sexual receptivity
a period of endometrial sloughing (menstruation)
timeline for the description of the cycle begins and ends with
menses, not ovulation or estrus
Lack of cyclicity = amenhorrea – absence of cyclicity for an
extended period of time in women of reproductive age (in
athletes-loss of body fat; lactation (prolactin ↓ GnRH frequency
and amplitude; menopause; undernutrition; stress)
Richardson et al., JCEM, 1987
Age in Years
1
10
100
1000
10000
100000
0 0 10 20 30 40 50 60
Women with regular
menses
perimenopausal
women
postmenopausal
women
B B
B B
B
J
F
F F
F
F
F
F
Prim
ord
ial F
olli
cle
s / O
va
ry
Ovarian follicle numbers with age
In women, the proliferative or follicular phase and the secretory or luteal phases of the menstrual cycle are of equal length.
The phases of the menstrual cycle are named for the changes that occur in the endometrium.
Follicular phase (estradiol dominated) = proliferative phase
Luteal phase (progesterone dominated) = secretory phase
Summary – comparison events that
occur between estrous and menstrual
cycles
Senger 2006
Steroidogenesis
• Ovary (Follicles and Corpus Luteum)
• Conceptus
• Fetal Adrenal
• Placenta
20a-Hydroxysteriod Dehydrogenase
20a-HSD
Progesterone 20a-dihydroprogesterone
NADPH NADP
H3C
O
O
H3C
OH
20a-HSD
Prolactin
Inhibits Enzyme
Does not support pregnancy
or decidualization in rodents
FSH is a glycoprotein. Each monomeric unit is a protein molecule with a sugar attached
to it; two of these make the full, functional protein. Its structure is similar to LH, TSH, and
hCG. The protein dimer contains 2 polypeptide units, labelled alpha and beta subunits.
The alpha subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino
acids. The beta subunits vary. FSH has a beta subunit of 118 amino acids (FSHB) that
confers its specific biologic action and is responsible for interaction with the FSH-
receptor.The sugar part of the hormone is composed of fucose, galactose, mannose,
galactosamine, glucosamine, and sialic acid, the latter being critical for its biologic half-
life. The half-life of FSH is 3-4 hours.
FSH
HORMONES FROM GRANULOSA CELLS OF FOLLICLE AND SERTOLI
CELLS OF TESTES THAT REGULATE FSH SECRETION
Inhibin: a peptide inhibitor of FSH synthesis and secretion
participates in regulation of estrous and menstrual cycles.
Structure: contains an alpha and beta subunit linked by disulfide
bonds. Two forms of inhibin differ in their beta subunits (A or B), while alpha
subunits are identical. Inhibin belongs to the transforming growth factor-β (TGF-
β) superfamily.
**********************************************************
Activin: a peptide stimulator of FSH synthesis and secretion
participates in regulation of estrous and menstrual cycles
Structure: two beta subunits identical to the two beta subunits (A or B)
of inhibin, allowing for the formation of three forms of activin: A, AB, and B;
linked by a single covalent disulfide bond.
**********************************************************
Follistatin: a single chain gonadal protein that inhibits FSH
synthesis and release by binding and antagonizing Activin.
LH is a dimeric glycoprotein with 2 polypeptide units, alpha and beta, connected
by two disulfide bridges
alpha subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino
acids.
beta subunits: LH beta subunit of 121 amino acids confers specific biologic
action and binding to LH receptor. This beta subunit identical to beta sub unit of
hCG and both bind LH receptor, but hCG beta subunit contains an additional 24
amino acids
half-life of LH is 20 minutes, shorter than that of FSH (3-4 hours) or hCG (24
hours).
LH
Prolactin is a single chain polypeptide of 199 amino acids with a molecular weight of
about 24,000 daltons. Its structure is similar to that of growth hormone and placental
lactogen. The molecule is folded due to the activity of three disulfide bonds.
PROLACTIN
Dopamine
pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly CONH2
GnRH
Prolactin Inhibiting Factor
OXYTOCIN
Oxytocin-Neurophysin
Maturase
Oxytocin + Neurophysin
Circulation
To Target
Tissues
Copyright ©2004 The Endocrine Society
Sherwood, O. D. Endocr Rev 2004;25:205-234
Relaxin: A Hormone with Diverse Actions in Rats
Copyright ©2004 The Endocrine Society
Sherwood, O. D. Endocr Rev 2004;25:205-234
FIG. 12. Influence of immune neutralization of circulating R1 relaxin throughout the second half of pregnancy on nipple development in rats
The Ovary
Progesterone receptors, PGR
Androgen
Primary
Primordial
Secondary
Preovulatory
Corpus luteum
LH receptors Granulosa cell
Atresia
Developing
Follicles
Ovulation
Theca (androgens)
Oocyte
(progesterone
estrogen)
Androgen Estrogen FSH receptors
Estrogen
FSH
receptors
Estrogen receptor alpha, ESR1
Steroidogenesis Before LH Surge
A
GL
BM
TI
TE
Ch P A2
Ch P A2 E2
E2
A: Antrum; GL: Granulosas; BM; Basement Memb
TI: Theca Int. TE: T Ext.; C: Capillaries Ch: Cholesterol; P: Progesterone; A2: Endrogen; E2: Estradiol
17a-HSD
P450scc
3-HSD
Arom
LH
FSH
P450scc
3-HSD
FSHR
LHCGR
EP
EP
Luteal Steroidogenesis
17a-HSD Ch P A2 E2 Arom
17a-HSD Ch P A2 E2 Arom
Ch: Cholesterol; P: Progesterone; A2: Endrogen; E2: Estradiol
(Some Species)
Large Luteal Cells
Small Luteal Cells
P450scc
3-HSD
P450scc
3-HSD
LHCGR
LHCGR and FSHR EP
EP
Estrogen production in the ovary:
collaboration between two cell types
aromatase
Primary steps leading
to the pre-ovulatory
LH surge
• In early follicular phase GnRH pulse
frequency increases
• Causes LH & FSH secretion
• Increase in E2 production
• E2 stimulates:
• increase in GnRH Receptors on
Gonadotrophs;
•increase in GnRH pulse frequency
•surge in GnRH leads to ovulatory
surge of LH
• The follicle then starts to secrete inhibin
– negative inhibitor of FSH
Portal vessels
bovine human
CL
LH surge
Primates
Fig. 9-2
Stigma of Ovarian Follicle of Chicken
Fig. 9-2
Fig. 9-2
LH SURGE, OVULATION
AND FERTILIZATION
Fig. 8-6
Events in Proteolytic Cascade for
Ovulation • LH and PGE2 induce plasminogen activator
(PA)
• Plasminogen is in follicular fluid
• PA converts Plasminogen to Plasmin, a serine
protease
• Plasmin converts procollagenase to
collegenase
• Combined effects of plasmin and collagenase
lead to rupture of stigma and ovulation
Adamts1 -A Disintegrin-like and
Metalloproteinase with
Thrombospondin Type 1 motif1
TSG6 - TNF-Alpha-induced
Protein 6
PCAP – pituitary activating
adenyl cyclase
PROAPOPTOTIC CASPASE
ADAPTOR PROTEIN
Tumor Necrosis Factor-stimulated Gene 6
IαI- Inter-alpha trypsin inhibitor
SHAP – IαI + hyaluronan (HA)
Follicle Wall and Ovulation • Stigma of Follicle – Avascular area at apex of follicle
– Proteases act to cause rupture of basement membrane
– Follicular fluid exits and takes oocyte and cumulus cells with
it into oviduct – Bernoulli’s Law
– Contractions of ovary generated by actin and myosin fibers
in area of theca externa aids in expulsion of oocyte and
cumulus cells
• Alpha adrenergic receptors on theca externa respond to
norepinephrine to enhance contractions
– Mature Graffian Follicle MINUS oocyte and cumulus cells
becomes corpus hemmorhagicum and with hyperplasia and
hypertrophy of large and small luteal cells they give rise to
the corpus luteum that produces progesterone
MECHANISM OF OVULATION – SEE PAPER
BY ESPEY
• LH, FSH and PGE2 act via LHCGR, FSHR and EPs to increase cAMP and Protein Kinase A that: – 1. Stimulates production of plasminogen activator by GC
and plasminogen activator converts plasminogen into plasmin (serine protease) and procollegenase to collagenase
– 2. Plasmin and Collagenase act on basement membrane and extracellular matrix of follicle to cause rupture and release of oocyte and cumulus cells
– 3. Ovulation is due to softening of cell wall, decrease in pressure in follicle, rupture of cell wall and as follicular fluid escapes it creates a negative pressure that pulls oocyte and cumulus mass with it into the infundibulum of the oviduct
Fig. 8-13
Follicular
Pressure
Does Not
Increase
Ovarian Histology • Corpus hemorrhagicum
(CH)/Corpora hemorrhagica – newly ruptured follicle
– essentially a blood clot
• Corpus luteum (CL)/Corpora lutea – LH stimulates formation
from theca interna and granulosa
– temporary endocrine gland
• progesterone
• Corpus albicans (CA)/Corpora albicantia – remains after CL regresses
LH Surge- Induced Events: The
Oocyte and Follicle • Inhibition of androgen and estrogen production
– Inhibition of C21 steroid 17α hydroxylase
– Aromatase enzyme inhibited
– Progesterone production increases
– Loss of FSHR on GC
– TC and GC become small and large luteal cells, respectively
• Hyperplasia
• Hypertrophy
• Endoplasmic reticulum develops in complexity
• Mitochondria develop with complex cristae to enhance conversion of
cholesterol to pregnenolone for P4 production
• Increase in cholesterol esters
LH Surge-Induced Events: Oocyte and
Follicle
• LHCGR and Prolactin receptors increase in
luteal cells to enhance LDL and HDL
receptors for uptake of cholesterol
• Progesterone Production Increases
• Increased production of PGE2 by luteal cells
Structural Changes During Luteinization
Antrum
GC
TC LC
BV
O
Small versus Large Luteal Cells
• LARGE LUTEAL CELLS FROM GC
– GREATER THAN 22 MICRONS
– HIGH BASAL P4 OUTPUT
– LITTLE ABUNDANT ROUGH ENDOPLASMIC
RETICULUM
• OXYTOCIN-NEUOPHYSIN
• RELAXIN
– FEW LHCGR
– ABUNDANT FP (PGF RECEPTORS)
Small versus Large Luteal Cells
• SMALL LUTEAL CELLS FROM TC
– 8 TO 22 MICRONS
– LOW BASAL P4 OUTPUT
– ABUNDANT LHCGR
– INCREASE P4 IN RESPONSE TO LH
– SMOOTH ENDOPLASMIC RETICULUM
• NO OXYTOCIN-NEUOPHYSIN
• NO RELAXIN
– FEW FP (PGF RECEPTORS)
Ovulation: Morphological and
Cytological Changes • Increase in Blood Flow to Follicle
– Histamines
– PGE2
– Increased Vascular Permeability to Proteins • Platelet Activating Factor
• Increased influx of plasminogen into follicular fluid
• Granulosa Cells – Loss of junctional complexes between corona radiata cells
and oocyte
– Increase in hyaluronic acid and water in cumulus GC
– High cAMP due to FSH, LH and PGE2
– Plasminogen Activator Enzyme activity increases to convert plasminogen to plasmin (active protease) and collegenase
Oocyte Maturation
• Pre-Meiosis: Prophase I arrest
– Oocyte-corona radiata cell communication via gap
junctions
– High cAMP in oocyte blocks meiosis
• Adenosine – Increases conversion of ATP to cAMP via
adenyl cyclase
• Hypoxanthine – decreases activity of phsphodiesterase that
converts cAMP to AMP
– Maturation Promoting Factor Inactive
– RNA synthesis – maternal RNA
LH SURGE-INDUCED EVENTS
• Changes in cytoplasmic mass
– Increase deposition of nutrients into oocyte by corona
radiata cell just before loss of gap junctions
– Nuclear Envelope Breakdown
– Breakdown of centrioles and chromosomes migrate to
periphery of oocyte
– Chromosomes individualize
– Chromosomes condense due to increase in histone I kinase
– Microtubule organizing center forms (Centriole and
Microtubules)
– Chromosomes align on equatorial plane at Metaphase I
– Polar Body I extruded
– Metaphase II arrest
– Nuclear Envelope Forms
Oocyte Maturation (Continued)
• Protein Synthesis
– Zona Pellucida Proteins
• ZP1 – Cross-linking
• ZP2 – Sperm Trap
• ZP3 – Sperm Receptor
– Cortical Granules
• Proteases – destroy sperm binding sites
• Colloidal Molecules: Hyaluronic Acid and
Glycosaminoglycans – bind water and increase space
between vitelline membrane and zona pellucida
• Structural Proteins – unknown function
Fig. 8-17
FERTILIZATION MEDIATED EVENTS
• Fertilization
– Increase in intracellular Ca++ in oocyte
– Germinal Vesicle Breakdown
– Microtubule Organizing Center with Spindle forms
– Metaphase II Completed
– Polar Body II extruded into perivitelline space
– Syngamy between male and female pronuclei
– Pairing of paternal and maternal chromosomes
– Nuclear envelope forms
– Zygote forms – 1- cell embryo
TIMING OF EVENTS AFTER LH
SURGE IN EWES
• 8-12H: PROPHASE I COMPLETED
• 12-20H: METAPHASE II
• 21-24H: POLAR BODY I EXTRUDED TO
PERIVITELLINE SPACE
• 24-30H: METAPHASE II AND OVULATION
• 30-36H: FERTILIZATION
Fig. 8-16
Summary
FSH & LH levels rise during early follicular phase stimulating
growth of early antral follicles
During mid follicular phase, selection and emergence of
dominant follicle occurs. Corresponds to an increase in E2
secretion.
Increasing estrogen levels stimulate GnRH, which results in
preovulatory surges of LH & FSH leading to ovulation.
Following ovulation, the corpus luteum secretes large amounts
of P4. The P4 inhibits GnRH synthesis and secretion by
neurons in the hypothalamus.