ROLE OF PROSTAGLANDINS IN
REPRODUCTIVE HEALTH
•GROUP 4
•PRESENTER: DR. FATUMA. M. SALAA
MEMBERS: DR. DAISY BOR, DR. CHRISTINE ONTIRIA,
DR. SYDNEY LUVAYO, DR.THIRIKWA GATHECA
Facilitator: Dr Kagema
OBJECTIVES
• Definition
• Chemistry & Nomenclature
• Biosynthesis
• Function and Source
• Physiological role in Female and Male reproductive system
• Role in pathological conditions in reproductive health
• Clinical uses
DEFINITION
• Prostaglandins are a group of
physiologically active compounds
generated enzymatically from Fatty
acids notably Arachidonic acid.
CHEMISTRY&NOMENCLATURE
CHEMISTRY: prostaglandins are 20- carbon carboxylic acids with
a cyclopentane ring which are formed from polyunsaturated
fatty acids.
NOMENCLATURE: Specific prostaglandins are named with a
letter (which indicates the type of ring structure) followed by a
number (which indicates the number of double bonds in the
hydrocarbon structure). For example, prostaglandin E1-series
1 is abbreviated PGE1and prostaglandin I2 - series 2-is
abbreviated PGI2.
BIOSYNTHESIS
FUNCTION OF PGS
• They have the property of acting as “local hormones”
• They sustain homeostatic function.
• They mediate pathological mechanisms including the inflammatory
response.
• Effects: vasodilation, vasoconstriction, stimulation of intestinal or
bronchial smooth muscle, uterine stimulation
SOURCE
ENDOGENOUS: Identified in the following:
FEMALE REPRODUCTIVE SYSTEM
Endometrium
Decidua and Amniotic membrane
Menstrual fluid
MALE REPRODUCTIVE SYSTEM
Seminal fluid
PHYSIOLOGICAL ROLE OF PGS
IN THE FEMALE REPRODUCTIVE
SYSTEM
• Ovulation
• Implantation
• Menstruation
• Labor
OVULATION
3 major phases in which PGs may be involved
a. Follicular maturation
b. Follicular rupture
c. Corpus luteum degeneration
IMPLATATION
• Prostaglandins participate in each stage of the interaction of the embryo
with the endometrium, for example in preimplantation, implantation
(apposition, adhesion/attachment, invasion/penetration) and
decidualization; as well as affecting many other cells and molecules.
• PGs have a complex role in each of these stages, e.g., the essential role
of prostaglandin E2 (PGE2) in the oocyte is to enhance the cumulus
expansion in ovulation for sperm penetration, to regulate extracellular
matrices disassembly, and also, importantly, to participate during
transport and embryo implantation.
• PGE2 maintains luteal function for embryo development and early
implantation. In addition, it induces chemokine expression for
trophoblast apposition and adhesion to the decidua for implantation.
FALLOPIANTUBE MOTILITY
Fallopian tubes can synthesise these PGs locally
PGE2
• Cause relaxation
• Suppresses its activity during & after ovulation
PGF2 a
• Causes contraction (facilitates ovum transport to the uterus)
PGI2
• Causes relaxation
MENSTRUATION
Different actions in the endometrium & myometrium
They affect blood flow in 3 different ways
• Direct effect on vascular smooth muscle-via PG receptors
• Increase in uterine tone or contractile activity-mechanical compression of
uterine arteries( PGE & PGF2 a)
• Potentiation/Depression of adrenergic neurotransmission ( PGE & PGF2
a )
• They alter local neurogenic release of norepinephrine from presynaptic
nerve terminals
• They modify responsiveness of postsynaptic nerve terminal to NE
MENSTRUATION
PGF2 a
• myometrial contraction (increase uterine contractility &
tone)
• Vasoconstriction (reduces uterine blood flow-ischemia
& menstrual flow ensues
PGE2
• Myometrial contraction
• Vasodilatation-increase in uterine blood flow
• Promotes platelet aggregation
MENSTRUATION
PGI2 (Prostacyclin)
• produced by endothelial cells
• Myometrial relaxation
• Vasodilatation
• Inhibits platelet activity-increased menstrual blood flow
NOTE: Elevation of Estrogen levels just before ovulation
stimulates PG activity which in turn produce their
vasoactive effects-mainly vasodilatation leading to increased
uterine blood flow.
LABOR
PGE2
• induces labor with cervical effacement and dilatation.
• It shortens induction to delivery interval.
• PGs promote myometrial contraction irrespective of the duration of
gestation, whereas oxytocin acts predominantly on the uterus at term or
in labor.
• Myometrial contraction (PGF2 more potent) Increased receptors of
PGE2, PGF2a and in turn increased sensitivity of myometrium to
oxtocin.
• Reduce Progesterone receptors (PGF2a)
• Placental separation
• Uterine involution (PGF2a)
Around term,
Increased Prostaglandin concentrations in Amniotic fluid
Increased COX expression in chorion
Increased sensitivity to PGs
Reduced PGDH activity more so in area of chorion laeve covering the
cervix. Usually high during pregnancy
• The parent fatty acid for omega-6 is linoleic acid (LA) and the parent fatty acid for omega-3
is -linolenic (ALA) acid.
α
• Both are essential Fatty acids. LA is converted to the biologically active omega-6 fatty acid,
arachidonic acid (AA), which is involved in cell-signaling pathways and functions as a
precursor for proinflammatory eicosanoids. ALA is converted to the biologically active
omega-3 fatty acid, EPA, which, in turn, is converted to the omega-3 fatty acid, DHA. DHA is
the critical component of cell membranes in the brain and retina, where it is involved in
visual and neural function as well as neurotransmitter metabolism.
• Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found
in plant and animal sources. They are synthesized endogenously in humans, though not
fully compensating all body requirements. Consequently, they are considered as partially
essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and
have several health benefits, including anti-inflammatory and anti-cancer characters.
RELATION OFTHE OMEGAS(3,6,9) TO PROSTAGLANDINS
• Diets that are balanced in both omega-6 and omega-3 may be less
inflammatory and immunosuppressive.
• A high ratio of omega-6 to omega-3 fatty acids will result in
increased proinflammatory eicosanoid production (ie,
prostaglandin E2 [PGE2] and prostaglandin F2α [PGF2α]). These
metabolites have been associated with the initiation of labor and
preterm labor.
• Including more EPA in the diet may lead to a reduction in the
production of proinflammatory eicosanoids and increased
production of prostacyclin (PGI2), which may promote
myometrial relaxation. Omega-3 fatty acids downregulate the
production of prostaglandins PGE2 and PGF2α, and may thereby
inhibit the parturition process.
The hypothesis that dietary supplementation of omega-3 fatty acids
could prevent preterm birth originated from studies conducted in the
Faroe Islands.31
Compared with the diet in Denmark, the population of
the Faroe Islands has a higher intake of marine foods, and babies born
to these women have higher birth weights (about 200 g) at term. In
fact, birth weights of babies from the Faroe Islands are higher than
those in 33 other countries.31
A number of randomized, controlled trials have attempted to validate
these findings, but with variable results. Four randomized, controlled
trials have demonstrated either a reduction in the rate of preterm
birth or an increase in the average length of gestation in either
primary or secondary analysis
Source:Pubmed:https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3046737/
MALE REPRODUCTIVE SYSTEM
• . PGs, above all PGE, occur in testicle tissue, have a
modulating effect on the LH-dependent steroid
synthesis and possibly influence sperm density and
sperm function. The PGs certainly play a part in the
motility of the vas deferens and participate
decisively in blood flow regulation in male genitals.
• The seminal vesicle synthesizes very large amounts of PGs,
which probably display their action in the semen plasma and
with this also in the female genital tract
MALE REPRODUCTIVE SYSTEM
• Smooth muscle relaxing prostaglandins such a PGE1
enhance penile erection by relaxing the smooth muscle of
the corpora cavernosa- Alprostadil used clinically in the
Diagnosis and second-line treatment of erectile dysfunction
due to vascular, psychological, or neurological etiologies.
• Men with a low seminal fluid concentration of PGs are
relatively infertile.
PATHOLOGICAL IMPLICATION OF
PGS
• Dysmenorrhea
Many of these patients have an increased synthesis of prostaglandins in their
endometrial tissue with increased prostaglandin release in the menstrual fluid.
The increased amount of prostaglandins induces incoordinate hyperactivity of
the uterine muscle resulting in uterine ischemia and pain.
NSAIDS such as ibuprofen, naproxen, flufenamic acid, mefenamic acid and
indomethacin are capable of relieving primary dysmenorrhea.These drugs are
inhibitors of the prostaglandin synthetase enzymes which are necessary for
prostaglandin biosynthesis.Thus, with ibuprofen it has been shown that clinical
relief of the dysmenorrheic symptoms accompanies the reduction of
menstrual fluid prostaglandins
PATHOLOGICAL IMPLICATION OF
PGS
• Endometriosis
Prostaglandin E(2) is up regulated in the peritoneal cavity in
endometriosis and is produced by macrophages and ectopic
endometrial cells. This abnormal prostaglandin production leads to
increased dysmenorrhea and early pregnancy losses in
endometriosis
PGE2 controls many critical functions, such as steroidogenesis,
angiogenesis, proliferation, and immune suppression that
contribute to the pathogenesis of endometriosis.
PATHOLOGICAL IMPLICATION OF
PGS
• Male Infertility
• Erectile Dysfunction
CLINICAL USES OF PGS IN
OBSTETRICS
• Cervical ripening prior to induction of labor or abortion.
• Induction of labor
• Augmentation of labor
• Management of Atonic Postpartum hemorrhage
• Termination of Molar pregnancy.
• Medical managent of tubal ectopic pregnancy
PREPARATIONS
PG E2- is available in the following forms:
Vaginal tablet-
Vaginal pessary
Gel- Prostin E(Dinoprostone)
PGE1-
Methyl ester of PGE1- Misoprostol
Note: Misoprostol is cheaper and stable at room temp unlike the
above PGE2
REFERENCES
• PUBMED
• DUTTA TEXTBOOK OF OBSTETRICS
• FIGO GUIDELINES ON INDUCTION OF LABOR

PROSTAGLANDINS IN REPRODUCTIVE HEALTH.pptx

  • 1.
    ROLE OF PROSTAGLANDINSIN REPRODUCTIVE HEALTH •GROUP 4 •PRESENTER: DR. FATUMA. M. SALAA MEMBERS: DR. DAISY BOR, DR. CHRISTINE ONTIRIA, DR. SYDNEY LUVAYO, DR.THIRIKWA GATHECA Facilitator: Dr Kagema
  • 2.
    OBJECTIVES • Definition • Chemistry& Nomenclature • Biosynthesis • Function and Source • Physiological role in Female and Male reproductive system • Role in pathological conditions in reproductive health • Clinical uses
  • 3.
    DEFINITION • Prostaglandins area group of physiologically active compounds generated enzymatically from Fatty acids notably Arachidonic acid.
  • 4.
    CHEMISTRY&NOMENCLATURE CHEMISTRY: prostaglandins are20- carbon carboxylic acids with a cyclopentane ring which are formed from polyunsaturated fatty acids. NOMENCLATURE: Specific prostaglandins are named with a letter (which indicates the type of ring structure) followed by a number (which indicates the number of double bonds in the hydrocarbon structure). For example, prostaglandin E1-series 1 is abbreviated PGE1and prostaglandin I2 - series 2-is abbreviated PGI2.
  • 5.
  • 6.
    FUNCTION OF PGS •They have the property of acting as “local hormones” • They sustain homeostatic function. • They mediate pathological mechanisms including the inflammatory response. • Effects: vasodilation, vasoconstriction, stimulation of intestinal or bronchial smooth muscle, uterine stimulation
  • 7.
    SOURCE ENDOGENOUS: Identified inthe following: FEMALE REPRODUCTIVE SYSTEM Endometrium Decidua and Amniotic membrane Menstrual fluid MALE REPRODUCTIVE SYSTEM Seminal fluid
  • 8.
    PHYSIOLOGICAL ROLE OFPGS IN THE FEMALE REPRODUCTIVE SYSTEM • Ovulation • Implantation • Menstruation • Labor
  • 9.
    OVULATION 3 major phasesin which PGs may be involved a. Follicular maturation b. Follicular rupture c. Corpus luteum degeneration
  • 10.
    IMPLATATION • Prostaglandins participatein each stage of the interaction of the embryo with the endometrium, for example in preimplantation, implantation (apposition, adhesion/attachment, invasion/penetration) and decidualization; as well as affecting many other cells and molecules. • PGs have a complex role in each of these stages, e.g., the essential role of prostaglandin E2 (PGE2) in the oocyte is to enhance the cumulus expansion in ovulation for sperm penetration, to regulate extracellular matrices disassembly, and also, importantly, to participate during transport and embryo implantation. • PGE2 maintains luteal function for embryo development and early implantation. In addition, it induces chemokine expression for trophoblast apposition and adhesion to the decidua for implantation.
  • 11.
    FALLOPIANTUBE MOTILITY Fallopian tubescan synthesise these PGs locally PGE2 • Cause relaxation • Suppresses its activity during & after ovulation PGF2 a • Causes contraction (facilitates ovum transport to the uterus) PGI2 • Causes relaxation
  • 12.
    MENSTRUATION Different actions inthe endometrium & myometrium They affect blood flow in 3 different ways • Direct effect on vascular smooth muscle-via PG receptors • Increase in uterine tone or contractile activity-mechanical compression of uterine arteries( PGE & PGF2 a) • Potentiation/Depression of adrenergic neurotransmission ( PGE & PGF2 a ) • They alter local neurogenic release of norepinephrine from presynaptic nerve terminals • They modify responsiveness of postsynaptic nerve terminal to NE
  • 13.
    MENSTRUATION PGF2 a • myometrialcontraction (increase uterine contractility & tone) • Vasoconstriction (reduces uterine blood flow-ischemia & menstrual flow ensues PGE2 • Myometrial contraction • Vasodilatation-increase in uterine blood flow • Promotes platelet aggregation
  • 14.
    MENSTRUATION PGI2 (Prostacyclin) • producedby endothelial cells • Myometrial relaxation • Vasodilatation • Inhibits platelet activity-increased menstrual blood flow NOTE: Elevation of Estrogen levels just before ovulation stimulates PG activity which in turn produce their vasoactive effects-mainly vasodilatation leading to increased uterine blood flow.
  • 16.
    LABOR PGE2 • induces laborwith cervical effacement and dilatation. • It shortens induction to delivery interval. • PGs promote myometrial contraction irrespective of the duration of gestation, whereas oxytocin acts predominantly on the uterus at term or in labor. • Myometrial contraction (PGF2 more potent) Increased receptors of PGE2, PGF2a and in turn increased sensitivity of myometrium to oxtocin. • Reduce Progesterone receptors (PGF2a) • Placental separation • Uterine involution (PGF2a)
  • 17.
    Around term, Increased Prostaglandinconcentrations in Amniotic fluid Increased COX expression in chorion Increased sensitivity to PGs Reduced PGDH activity more so in area of chorion laeve covering the cervix. Usually high during pregnancy
  • 18.
    • The parentfatty acid for omega-6 is linoleic acid (LA) and the parent fatty acid for omega-3 is -linolenic (ALA) acid. α • Both are essential Fatty acids. LA is converted to the biologically active omega-6 fatty acid, arachidonic acid (AA), which is involved in cell-signaling pathways and functions as a precursor for proinflammatory eicosanoids. ALA is converted to the biologically active omega-3 fatty acid, EPA, which, in turn, is converted to the omega-3 fatty acid, DHA. DHA is the critical component of cell membranes in the brain and retina, where it is involved in visual and neural function as well as neurotransmitter metabolism. • Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They are synthesized endogenously in humans, though not fully compensating all body requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including anti-inflammatory and anti-cancer characters. RELATION OFTHE OMEGAS(3,6,9) TO PROSTAGLANDINS
  • 19.
    • Diets thatare balanced in both omega-6 and omega-3 may be less inflammatory and immunosuppressive. • A high ratio of omega-6 to omega-3 fatty acids will result in increased proinflammatory eicosanoid production (ie, prostaglandin E2 [PGE2] and prostaglandin F2α [PGF2α]). These metabolites have been associated with the initiation of labor and preterm labor. • Including more EPA in the diet may lead to a reduction in the production of proinflammatory eicosanoids and increased production of prostacyclin (PGI2), which may promote myometrial relaxation. Omega-3 fatty acids downregulate the production of prostaglandins PGE2 and PGF2α, and may thereby inhibit the parturition process.
  • 20.
    The hypothesis thatdietary supplementation of omega-3 fatty acids could prevent preterm birth originated from studies conducted in the Faroe Islands.31 Compared with the diet in Denmark, the population of the Faroe Islands has a higher intake of marine foods, and babies born to these women have higher birth weights (about 200 g) at term. In fact, birth weights of babies from the Faroe Islands are higher than those in 33 other countries.31 A number of randomized, controlled trials have attempted to validate these findings, but with variable results. Four randomized, controlled trials have demonstrated either a reduction in the rate of preterm birth or an increase in the average length of gestation in either primary or secondary analysis Source:Pubmed:https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3046737/
  • 21.
    MALE REPRODUCTIVE SYSTEM •. PGs, above all PGE, occur in testicle tissue, have a modulating effect on the LH-dependent steroid synthesis and possibly influence sperm density and sperm function. The PGs certainly play a part in the motility of the vas deferens and participate decisively in blood flow regulation in male genitals. • The seminal vesicle synthesizes very large amounts of PGs, which probably display their action in the semen plasma and with this also in the female genital tract
  • 22.
    MALE REPRODUCTIVE SYSTEM •Smooth muscle relaxing prostaglandins such a PGE1 enhance penile erection by relaxing the smooth muscle of the corpora cavernosa- Alprostadil used clinically in the Diagnosis and second-line treatment of erectile dysfunction due to vascular, psychological, or neurological etiologies. • Men with a low seminal fluid concentration of PGs are relatively infertile.
  • 23.
    PATHOLOGICAL IMPLICATION OF PGS •Dysmenorrhea Many of these patients have an increased synthesis of prostaglandins in their endometrial tissue with increased prostaglandin release in the menstrual fluid. The increased amount of prostaglandins induces incoordinate hyperactivity of the uterine muscle resulting in uterine ischemia and pain. NSAIDS such as ibuprofen, naproxen, flufenamic acid, mefenamic acid and indomethacin are capable of relieving primary dysmenorrhea.These drugs are inhibitors of the prostaglandin synthetase enzymes which are necessary for prostaglandin biosynthesis.Thus, with ibuprofen it has been shown that clinical relief of the dysmenorrheic symptoms accompanies the reduction of menstrual fluid prostaglandins
  • 24.
    PATHOLOGICAL IMPLICATION OF PGS •Endometriosis Prostaglandin E(2) is up regulated in the peritoneal cavity in endometriosis and is produced by macrophages and ectopic endometrial cells. This abnormal prostaglandin production leads to increased dysmenorrhea and early pregnancy losses in endometriosis PGE2 controls many critical functions, such as steroidogenesis, angiogenesis, proliferation, and immune suppression that contribute to the pathogenesis of endometriosis.
  • 25.
    PATHOLOGICAL IMPLICATION OF PGS •Male Infertility • Erectile Dysfunction
  • 26.
    CLINICAL USES OFPGS IN OBSTETRICS • Cervical ripening prior to induction of labor or abortion. • Induction of labor • Augmentation of labor • Management of Atonic Postpartum hemorrhage • Termination of Molar pregnancy. • Medical managent of tubal ectopic pregnancy
  • 27.
    PREPARATIONS PG E2- isavailable in the following forms: Vaginal tablet- Vaginal pessary Gel- Prostin E(Dinoprostone) PGE1- Methyl ester of PGE1- Misoprostol Note: Misoprostol is cheaper and stable at room temp unlike the above PGE2
  • 29.
    REFERENCES • PUBMED • DUTTATEXTBOOK OF OBSTETRICS • FIGO GUIDELINES ON INDUCTION OF LABOR

Editor's Notes

  • #2 Clinical implications of PGs in RH
  • #3 Prostaglandins (PGs) are lipid mediators, generated from arachidonic acid (AA) metabolism via cyclooxygenases (COX). They were discovered in the 1930s as regulators of blood pressure and smooth muscle contraction [1]. The distribution of synthases and receptors for each PG is different in various cell types, and PGs are activated via either paracrine or autocrine signaling on the surface of each cell type. PGs bridge the interactions between various immune-modulating cells, and are considered key players in regulating pro-inflammatory and anti-inflammatory responses
  • #5 Figure 1The cyclooxygenase pathway. Extracellular agonists bind to cell-surface receptors and thereby activate phospholipases that liberate arachidonate from membrane phospholipids. Cyclooxygenase, either COX-1 or COX-2, then catalyses the formation of prostaglandin H2 (PGH2). Other enzymes then from the specific products prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane A2 (TXA2).
  • #16 Although both F and E series prostaglandins result in uterine contractions, E series prostaglandins are relatively more uteroselective and are clearly superior to F series prostaglandins in producing cervical ripening.
  • #17 What is the full form of PGDH? The prostaglandin (PG)-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) is highly expressed in the chorion leave
  • #18 an essential fatty acid for animals because they cannot synthesize it, in contrast to plants, which can synthesize it from oleic acid.
  • #19 Linoleic acid is abundant in many nuts, fatty seeds and their derived vegetable oils. Fish and other seafood contain long-chain omega-3 polyunsaturated fatty acids (PUFA), which are essential nutrients
  • #21 PGs, above all PGE, occur in testicle tissue, have a modulating effect on the LH-dependent steroid synthesis and possibly influence sperm density and sperm function. The PGs certainly play a part in the motility of the vas deferens and participate decisively in blood flow regulation in male genitals.
  • #27 PGE2Important in dysmenorrhea (blocked by NSAIDs)PGI2 and high concentrations of PGE2 cause relaxationPGF2 together with oxytocin is essential for onset of parturition