Animal Science 434

1
Animal Science 434

• Lecture 11 The Luteal Phase of the Estrous and
  Menstrual Cycle

2
Ovulation
Ovulation
Luteal Phase
CL Formation (Metestrus)
Follicular Phase
P4 Production (Diestrus)
Relative Progesterone Levels (Blood)
Luteolysis
3

• steroid synthesis
• progesterone
• collagenase
• theca interna

4

• present 1-3 days following ovulation
• blood vessels in follicle wall rupture
• walls collapse
• cells intermix
• old basement membrane becomes connective tissue
  of CL

5

• increases in size
• papilla forms
• composed of cells from the granulosa and theca
  interna
• progesterone production increases
• a small cavity may be present where the
  folliclular antrum was present

6
Luteal Tissue

• Large cells from granulosa
• Small cells from the theca interna

7
(No Transcript)
8
Mitochondria
Secretory Granules
- Oxytocin - Relaxin
9
Functional Capability of CL

• the number of luteal cells
• large cells undergo hypertrophy (3 fold)
• small cells undergo hyperplasia (5 fold)
• vascularization of CL
• Initiated by angiogenic factors from follicle
• Vascularity effects CL steroid synthesis and
  delivery of hormones
• Insufficient CL function
• Failure to maintain pregnancy
• Important in domestic animals

10
Blocks Estrus Negative Feedback
Progesterone Targets
Aveolar Development
11
Molecular Mechanism of LH on Luteal Cell
(cAMP second messenger)
G
Plasma Membrane
Receptor
PKA
R
C
S-ER Steroid Synthesis
( PO4)
Mitochondria
Cholesterol
Pregnenolone
Cholesterol
Protein
R-ER Protein Synthesis
Synthesis
(Enzymes)
12
Molecular Mechanism of LH on Luteal Cell
(cAMP second messenger)
G
Plasma Membrane
Receptor
PKA
R
C
S-ER Steroid Synthesis
Chol-Ester
( PO4)
LDL
Mitochondria
Chol Esterase
Cholesterol
Pregnenolone
Cholesterol
Protein
R-ER Protein Synthesis
Synthesis
(Enzymes)
13
Luteolysis

• Uterus
• PGF2a
• Oxytocin

14
Luteolysis in Cows, Ewes, Sows
TotalHysterectomy
NormalUterus
CL
CL LifespanLonger
CL Normal Lifespan
Similar to Gestation Length
IpsilateralHysterectomy
ContralateralHysterectomy
CL LifespanLonger
CL Normal Lifespan
gt35 days
15
Luteolysis

• Uterus
• PGF2a
• Oxytocin

16
Prostaglandin F2a Control of Luteolysis
Uterine Horn
Progesterone from CL stimulates production of
uterine PGF2a after day 15 in cow
Corpus Luteum
Oviduct
Ovary
Uterine Vein
Ovarian Pedicle
PGF
PGF2a is picked up by ovarian artery through
counter current exchange and delivered back to
the ovary where it causes lysis of the CL
PGF into Artery
Uterine Artery
17
TotalHysterectomy
NormalUterus
CL
CL NormalLifespan
CL Maintained
Luteolysis Mare
IpsilateralHysterectomy
ContralateralHysterectomy
50 of CLs Maintained
50 of CLs Maintained
18
Blood Supply to Uterus and Ovary in the Mare
19
PGF Not Effective (Sow)
PGF Not Effective (Cow, Ewe, Mare)
20
Luteolysis

• Uterus
• PGF2a
• Oxytocin

21
(No Transcript)
22
(No Transcript)
23
Relationship of Oxytocin and PGF2a
Posterior Pituitary
Anterior Pituitary
CL
Ovary
Uterus
24
Luteolysis

• decreased blood flow
• cellular response
• apoptosis
• progesterone synthesis
• Immune response
• Lymphocytes
• Macrophages

25
Molecular Mechanism of PGF (Ca2 Second
Messenger)
PGF
Plasma Membrane
Receptor
Cholesterol
Ca2
Endoplasmic Reticulum
Apoptosis
Progesterone
Plasma Membrane
26
Luteolysis

• decreased blood flow
• cellular response
• apoptosis
• progesterone synthesis
• Immune response
• Lymphocytes
• Macrophages

27
Menstrual Cycle
28
Anterior Pituitary Hormones
LH
FSH
Progesterone
Ovarian Hormones
Estradiol
Ovulation
Corpus Albicans
Follicle
Corpus Luteum
Ovary
Dominance
Selection
Uterine Endo- metrium
2
4
6
8
10
14
16
18
20
22
24
26
28
2
12
29
Luteolysis in the Primate

• Does not require the uterus
• CL lifespan in the human is 12-14 days unless
  pregnancy occurs
• In the absence of pregnancy, CL self destructs
• Possible intra-ovarian oxytocin receptors and
  PGF2a production
• Menstruation
• Drop in P4 and E2
• Endometrial PGF2a, vasoconstriction, necrosis
• Endometrial inflammation and tissue degeneration

30
Manipulating Ovulation

• Hormonal induction of ovulation
• PGF2a
• GnRH
• Progestins
• Superovulation
• FSH
• eCG

31
Principle of PGF2a Use

• Regress active corpus luteum
• Only effective on a day 5 - 17 CL
• Not effective on days
• 1 - 4 (CL not responsive)
• 18 - 21 (CL already regressed)

32
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
33
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
34
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
35
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
36
Ovsynch
GnRH
PGF2?
GnRH
7 Days
36 - 48 hours
Eliminate current follicular wave
Luteolysis
Ovulates dominant follicle
37
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
38
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
39
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
40
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
41
Induction of Ovulation with PGF2a
Progesterone
Follicular Size
9
16
21
Ovulation
Day After Ovulation
42
Ovsynch
GnRH
PGF2?
GnRH
7 Days
36 - 48 hours
Eliminate current follicular wave
Luteolysis
Ovulates dominant follicle
43
Use of Progestogens

• Principle
• Maintain the cow under the influence of
  progesterone until corpus luteum regresses,
  remove progesterone -
• animal respond to progesterone with estrus and
  ovulation 2-5 days later.
• Administration
• Injection
• Feed
• Implant
• Pessary or Control Internal Drug Release
  (CIDR)

This does not regress the CL!!!!
44
Progestens Effect on Ovulation
Progesterone From C.L.
Ovulation
Ovulation
Estrus
Estrus
17
21
0
Follicular Wave
Follicular Wave
Follicular Wave
45
Progestens Effect on Ovulation
Progesterone From C.L.
Ovulation
Ovulation
Estrus
Estrus
Ov.
17
21
0
Follicular Wave
Follicular Wave
Follicular Wave
Remove CIDR
P4 from CIDR
P4 from CL
Estrus
Estrus
17
21
0
Follicular Wave
Follicular Wave
Follicular Wave
46
Stimulating Follicular Development
eCGorFSH
Multiple Ovulations
Ovulation
Estrus
Estrus
Progesterone From C.L.
PGF2a
17
eCG orFSH
Estrus
Estrus
First Follicular Wave
10-12