Ovarian function in ruminants

1
Ovarian function in ruminants

• B. Berisha and D. Schams

2
Follicle Development and Ovulation

• Kelley Chiles
• Team 4
• ANSC 630
• September 9, 2009

3
Follicular Growth
Senger 2003
IGF SystemInsulin-like Growth Factor IGFBPIGF
Binding Protein IGFBP-4 Protease
4
Ovarian Angiogenesis

• VEGFinduces plasminogen activators,
  angiogenesis
• FGF-2endothelial growth, synergistic effects of
  angiogenic growth factors
• IGF, VEGF, and ANTP are important for follicle
  maturation

Fig. 1 Schematic presentation of proposed
actions of intrafollicular hormones and growth
factors in mature bovine follicle
5
Angiogenic Factors

• VEGF
• mRNA expression increases in follicle tissue and
  follicular fluid with developmental stage of
  follicular growth
• VEGF receptor expression does not change during
  final follicle growth
• FGF
• FGF-1 mRNA expression is higher in the TI and
  lower in GC, no change during final follicular
  growth
• FGF-1 protein is found in cytoplasm of GC, smooth
  muscle cells of blood vessels, TI (smaller
  amount)
• FGF-2 mRNA expression increases in the TI in
  larger follicles
• FGFR in TI increases at the beginning of
  estradiol production

6
Angiogenic Factors

• IGF
• IGF-1 expression is high in the TI before
  selection increases in GC after selection
• IGF-2 expression is constant in the TI
• ANPT
• ANPT-12 and their receptors (Tie12) are
  expressed in the TI, Tie receptors low in GC
• ANPT-2 decreases in the TI and GC in mature
  follicles, vasculature was stable/mature

7
Ovulation
Adapted from Senger 2003
8
References

• Berisha, B., Schams, D. 2005. Ovarian function in
  ruminants. Dom Animal Endocrin. 29, 305-317
• Pathways to Pregnancy and Parturition. Senger,
  PL.2003. 2nd Revised Ed.
• Fortune, J.E., River, G.M., Yang, M.Y. 2004.
  Follicular development the role of the
  follicular microenvironment in the selection of
  the dominant follicle. Animal Reproduction
  Science. 82-82, 109-126

9
Corpus Luteum and Growth Factors

• Will Dickison
• Team 4
• ANSC 630
• September 9, 2009

10
CL formation

• Series of morphological and biochemical changes
  of the TI and GC of the preovulatory follicle.
• Changes are termed luteinization, take place
  after LH surge.
• Heterogenous tissue consisting of EC, LLC and
  SLC.

11
Corpus Luteum Function

• Two primary Hormones support function of CL, they
  are LH and GH.
• Lh is the principal hormone stimulating release
  of P4 from the SLC, as most of the LHr are
  located on the SLC.
• Although 80 of the total output of P4 is from
  the LLC. (in vitro studies)
• Receptors for GH and IGF-1 are only found on LLC
  could be needed for high basal levels of P4 from
  LLC.

12
Stimulation of the Angiogenic factors

• Angiotensin II and Endothelin-1 both stimulate
  VEGF and FGF-2.
• AngII is generated in two steps-renin catalyzes
  angiotensinogen to ANGI, then Ang-I is hydrolyzed
  by ACE to yield Ang-II.
• Induces VEGF expression in the EC, and increases
  Vegf angiogenic activity by upregulating VEGFR-2.
• Ang-II is the highest concentration after
  ovulation decreases mid-luteal, increases
  late-luteal and is lowest during regression

13
Endothein-1

• Derived from pre-proendothelins, it is then
  proteolytically processed by endopeptidases.
• Et-1 is inactive until cleaved by ECE-1
• ET-1 as well as Ang-II regulate FGF-2 production
  in the endothelial cells
• Et-1 is high very early luteal phase, very low
  mid and late luteal but reaches its peak during
  regression

14
Ang-II and ET-1 other role

• Play a major role in functional luteolysis by
  decreasing blood flow 8-24 hours after luteolytic
  dose of pgf2alpha.
• Also play a role in structural luteolysis by
  inducing apoptosis and necrosis of luteal cells.

15
Oxytocin and Luteolysis

• Jason McKnight
• Team 4
• ANSC 630
• September 9, 2009

16
Oxytocin- A review

• Peptide hormone
• Produced in hypothalamus and stored in the
  neurohypophysis
• Also produced by CL
• Causes smooth muscle contractions, milk letdown,
  regulates luteolysis by promoting PGF2a synthesis
  in uterus
• PGF2 a is THE luteolysin

17
Oxytocin in Ruminants

• In the functional CL, large luteal cells
  (previously granulosal cells) contain large
  numbers of dense secretory granules close to the
  plasma membrane.
• During normal cycling, these granules contain
  oxytocin

18
Luteolysis

• Regression/Disintegration of CL and luteal tissue
• Controlled by OT and P4 from CL , OT from CL, and
  PGF2a from uterus
• P4 prevents formation of OT Receptors, but after
  10 to 12 days, it loses its ability to block
  formation.
• OT then causes the release of PGF2a from the
  endometrium
• Positive feedback mechanism
• Mechanism still not well known

19
(No Transcript)
20
References

• Pathways to Pregnancy and Parturition. Senger,
  PL.2003. 2nd Revised Ed.
• Berisha, B., Schams, D. Ovarian function in
  ruminants. Dom Animal Endocrin. 29(2005) 305-317
• McCracken, J.A., Custer, E.E., Lamsa, J.C.
  Luteolysis A neuro-endocrine mediated event.
  Phys. Rev. 79 (1999) 263-324

21
Growth Factors Luteolysis

• Kendrick Sudderth
• Team 4
• ANSC 630
• September 9, 2009

22
Growth (Survival) Factors

• IGF insulin-like growth factor
• VEGF vascular endothelial growth factor
• FGF fibroblast growth factor

23
IGF

• Polypeptide hormone
• Action promotes cell proliferation, inhibits cell
  death (apoptosis).
• Development of early CL
• Indirect promotion of angiogenesis through
  stimulation of VEGF production
• Stimulates proliferation and differentiation of
  EC
• Luteinization of granulosa-lutein cells
• Stimulates oxytocin and progesterone production
• mRNA expression
• highest in early luteal phase (d 1-4)
• decreased in mid to late luteal phase.
• Receptors greatest expression in large LCs.
• Six binding proteins expressed (IGFBPs).
• Luteolysis IGF-2 ?, IGFR-1 ?, IGFBF-1,5 ?,
  IGFBP-3,4 ?

24
FGF

• FGF-2 important for endothelial growth,
  synergistic growth with VEGF.
• FGF-2 expression highest in very early luteal
  phase (d 1-2)
• FGFR highest d 1-4
• FGF-2 in tissue high during early and late luteal
  phase
• significant decrease d 5-7
• Differential location different function
• FGF-1 LC - mid luteal and regression
• FGF-2 capillary EC and smooth muscle cells of
  arteries - early luteal
• Maximal up-regulation of FGF-1 and 2 during
  functional luteolysis (until 12 hr)
• Contributes to functional luteolysis
• Luteolysis FGF-2 ?

25
VEGF

• Protein known to increase mitosis and migration
  of endothelial cells
• Works in concert with ANPT-Tie
• Determines outcome of instability created by high
  ANPT-2/1 ratio
• ? VEGF form new vascular network angiogenesis
• ? VEGF regression of vascular network
  angiolysis
• Found primarily in LCs
• mRNA and protein levels
• highest during early luteal stage (d 1-7)
• significantly lower in mid to late luteal phase
• protein level significantly decreased 2 hours
  post PG
• Significant down-regulation of mRNA expression
• for VEGF and its two receptors 12 hours post PG
• (structural luteolysis)
• Lack of VEGF contributes to structural luteolysis
• Luteolysis VEGF ?

26
Fig. 2. Schematic presentation of expression
profiles of ANPT-2 to ANPT-1 ratio (black bars)
and angiogenic factor VEGF (white bars) in bovine
corpus luteum during corpus luteum formation,
function and luteolysis.
From Berisha, B. and Schams, D. 308
27
Fig. 3. Schematic presentation of factors
possibly involved in luteolysis in cow.
From Berisha, B. and Schams, D. 312
28
Summary

• IGFs work as a complex part of the luteolytic
  cascade.
• Decline in VEGFs contribute to structural
  luteolysis.
• FGFs contribute to functional luteolysis.

29
References

• Berisha, B., Schams, D. 2005. Ovarian function in
  ruminants. Dom Animal Endocrin. 29, 305-317
• Pathways to Pregnancy and Parturition. Senger,
  PL.2003. 2nd Revised Ed.

30
Questions?