PROSTAGLANDINS IN PRIMATE OVULATORY FOLLICLES

Summary

Principal Investigator: DIANE DUFFY
Abstract: DESCRIPTION: Preliminary studies conducted by the PI indicate that the ovulatory gonadotropin surge initiates prostaglandin (PG) production by the primate periovulatory follicle and the injection of a PG synthesis inhibitor directly into the follicle prevents follicle rupture without altering normal luteal progression. The proposed studies will address the hypothesis that PGs produced by the preovulatory follicle act locally to regulate specific molecular events related to follicular rupture, but not luteinization, of the primate follicle. Experiments are proposed to examine the locations and gonadotropin regulation of PG synthetic enzymes within the primate periovulatory follicle (Specific Aim 1). In vitro protocols will be used to determine if gonadotropin stimulation of granulosa and/or theca cells of the follicle is sufficient to initiate PG synthesis (Specific Aim 2). PG receptors will be localized to cells of the periovulatory follicle to determine the site(s) of PG action (specific Aim 3). PG-stimulated expression of molecular markers of follicle rupture (matrix metalloproteinases and their inhibitors [TIMPs], plasminogen activator and its inhibitor and luteinization (3beta hydroxydehydrogenase, steroidogenic acute regulatory protein [STAR], vascular endothelial growth factor (VEGF], angiopoietin-1 and 2) will be assessed (specific Aim 4). Immunocytochemistry and in situ hybridization will be used to localize PG synthetic enzymes and PG receptors to the cells of the preovulatory follicle. Gonadotropin regulation of mRNAs for PG synthetic enzymes will be determined by semi-quantitative RT-PCR based assays. PG production of cultured ovarian cells and tissues will be measured using EIA kits. In vitro expression of markers of follicular rupture/luteinization will be assessed using RT-PCR based assays for mRNAs, ELISA kits for enzyme proteins and angiogenic factors, and RIA for media progesterone. Intrafollicular injection of PG synthesis inhibitor will be used to determine if PGs regulate specific markers of follicular rupture and luteinization in vivo. These studies will likely demonstrate that the mid cycle gonadotropin surge initiates PG synthesis by primate ovarian follicle through the induction of specific enzymes and support the hypothesis that PGs act locally to trigger specific processes related to ovulation, but not luteinization, of the periovulatory follicle. This may provide insight into the mechanisms leading to infertility (e.g., leuteinized unruptured follice syndrome) and support the developoment of PG synthesis inhibitors of PG synthesis inhibitors for use as contraceptives.
Funding Period: 2001-02-15 - 2005-08-31
more information: NIH RePORT

Top Publications

  1. ncbi Adipose differentiation-related protein: a gonadotropin- and prostaglandin-regulated protein in primate periovulatory follicles
    Carrie L Seachord
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA
    Biol Reprod 72:1305-14. 2005
  2. ncbi Microsomal prostaglandin E synthase-1 (mPGES-1) is the primary form of PGES expressed by the primate periovulatory follicle
    Diane M Duffy
    Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, VA 23507, USA
    Hum Reprod 20:1485-92. 2005
  3. ncbi An ovulatory gonadotropin stimulus increases cytosolic phospholipase A2 expression and activity in granulosa cells of primate periovulatory follicles
    Diane M Duffy
    Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, Virginia 23507, USA
    J Clin Endocrinol Metab 90:5858-65. 2005
  4. pmc Comparative maturation of cynomolgus monkey oocytes in vivo and in vitro
    Hang Yin
    The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynaecology Eastern Virginia Medical School, Norfolk, VA 23507, USA
    Reprod Biol Endocrinol 4:14. 2006
  5. ncbi Primate granulosa cell response via prostaglandin E2 receptors increases late in the periovulatory interval
    Nune Markosyan
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507 1980, USA
    Biol Reprod 75:868-76. 2006
  6. ncbi Prostaglandin-endoperoxide synthase (PTGS1 and PTGS2) expression and prostaglandin production by normal monkey ovarian surface epithelium
    Rafael A Cabrera
    The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia, USA
    Fertil Steril 86:1088-96. 2006
  7. pmc Two pathways for prostaglandin F2 alpha synthesis by the primate periovulatory follicle
    Brandy L Dozier
    Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, Virginia 23507, USA
    Reproduction 136:53-63. 2008

Scientific Experts

Detail Information

Publications7

  1. ncbi Adipose differentiation-related protein: a gonadotropin- and prostaglandin-regulated protein in primate periovulatory follicles
    Carrie L Seachord
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA
    Biol Reprod 72:1305-14. 2005
    ..Because ADRP facilitates arachidonic acid uptake in non-ovarian cells, ADRP-associated lipid droplets may enhance arachidonic acid uptake by granulosa cells to provide a precursor for periovulatory prostaglandin production...
  2. ncbi Microsomal prostaglandin E synthase-1 (mPGES-1) is the primary form of PGES expressed by the primate periovulatory follicle
    Diane M Duffy
    Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, VA 23507, USA
    Hum Reprod 20:1485-92. 2005
    ..Follicular PGE2 levels increase just before the expected time of ovulation, suggesting that the midcycle LH surge induces the expression of enzymes involved in PGE2 synthesis...
  3. ncbi An ovulatory gonadotropin stimulus increases cytosolic phospholipase A2 expression and activity in granulosa cells of primate periovulatory follicles
    Diane M Duffy
    Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, Virginia 23507, USA
    J Clin Endocrinol Metab 90:5858-65. 2005
    ..Arachidonic acid, the common precursor for PG synthesis, is cleaved from membrane phospholipids via the activity of phospholipase A2 (PLA2)...
  4. pmc Comparative maturation of cynomolgus monkey oocytes in vivo and in vitro
    Hang Yin
    The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynaecology Eastern Virginia Medical School, Norfolk, VA 23507, USA
    Reprod Biol Endocrinol 4:14. 2006
    ....
  5. ncbi Primate granulosa cell response via prostaglandin E2 receptors increases late in the periovulatory interval
    Nune Markosyan
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507 1980, USA
    Biol Reprod 75:868-76. 2006
    ....
  6. ncbi Prostaglandin-endoperoxide synthase (PTGS1 and PTGS2) expression and prostaglandin production by normal monkey ovarian surface epithelium
    Rafael A Cabrera
    The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia, USA
    Fertil Steril 86:1088-96. 2006
    ..To determine whether hCG regulates the expression of prostaglandin (PG) synthesis enzymes and the production of PGs by normal monkey ovarian surface epithelium (OSE)...
  7. pmc Two pathways for prostaglandin F2 alpha synthesis by the primate periovulatory follicle
    Brandy L Dozier
    Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, Virginia 23507, USA
    Reproduction 136:53-63. 2008
    ..Both of these enzyme activities are present in periovulatory granulosa cells. These data support the concept that follicular PGF2 alpha can be synthesized via two pathways during the periovulatory interval...