Some Functions Of Prostaglandin E2 In Early Pregnancy

Some Functions Of Prostaglandin E2 In Early Pregnancy

Although we attempt to make the case for maternal serum Prostaglandin E2 being a cause of pregnancy sickness, we realise that no attempt should be made to reduce the synthesis of Prostaglandin E2 in early pregnancy because of the vital functions of Prostaglandin E2 at that time. These functions include: 

A. Immunosuppression of Decidual CD-16 CD56 Bright NK Cells (LGL White Cells)

Uterine large granulated lymphocytes (LGL), constitute 70% of the decidual white cells,
together with macrophages 20% and CD+3 T Cells 10%.  Peripheral LGLs  respond to
Interleukin-2 (IL-2) by proliferating and becoming potent lymphokine activated killer cells
capable of greatly increased killing of K 562 cells (1) and human trophoblast cells (2).
These decidual CD-16 CD56 Bright NK cells possess a high affinity receptor for IL-2.  These
NK cells have both Interleukin-2 receptors alpha and beta (3).  Their NK (killer) activity is
markedly elevated even by treatment with small amounts of IL-2 (3).  Therefore, there
needs to be suppression of IL-2 at the feto-maternal interface.
 
 Prostaglandin E2 inhibited T lymphocyte proliferation by 80-90% of control values.  This
was associated with a similar degree of inhibition of IL-2 production while the expression
of IL-2 receptors was not affected.  This was in marked contrast to the expression of the
transferrin receptor, which was inhibited 65% after 72 hours of in vitro action (4).  These
studies demonstrate that Prostaglandin E2 exerts its inhibitory effect on T cell activation and
proliferation via two distinct pathways; inhibition of IL-2 production and inhibition of
transferrin receptor expression.  The transferrin receptor expression is mediated via the
c’AMP pathway and is IL-2 dependent. (4)  
For additional information see section Presence of Prostagladins E2 in Decidua.



B. Stimulation of Cyclic AMP Levels in Immature Placental Villi

The presence of Prostaglandin E2 in the culture medium evoked a glycogenolytic effect in
immature human placental villi, 8-20 weeks placentae used, including the increase in tissue
cyclic AMP levels.  The effects of 10mg/ml Prostaglandin E2 were more marked than those
of hCG on activation of phosphorylase.   Prostaglandin E2 induced a larger decrease in
placental glycogen and a 149% increase in cyclic AMP concentration in immature placental
tissue.  (5)
 
 The fact that Prostaglandin E2 stimulates c’AMP and glycogenolysis has significant effects
on trophoblast cells as c’AMP mediates the action of a wide variety of hormones on target
tissues.  (6)
 
 Prostaglandin E2 has other functions in early pregnancy, for example, the synthesis of
matrix metalloproteinases which assist cytotrophoblast invasion of the decidua is partly
dependent upon PGE2 production (7).  However, the two significant functions mentioned
above alone serve to show the importance of Prostaglandin E2 in early pregnancy.  
Therefore, any attempt to improve pregnancy sickness by reducing Prostaglandin E2
synthesis in early pregnancy could adversely effect that pregnancy.

REFERENCES

1. LOKE Y W, KING A.

 Recent developments in the human maternal-fetal immune interations.

 Current Opinion in Immunology. 1991;3:762-766.

2. KING A, LOKE Y W.

 Human trophoblast and JEG choriocarcinoma cells are sensitive to Lysis by IL-2- stimulated decidual NK cells.

 Cell Immuno. 1990;129:435-448.


3. SAITO S, MORII T, ENOMOTO M, SAKAKURA S, NISHIKAWA K,

 NARITA N, ICHIJO M.

The effect of Interleukin-2 and transforming growth factor B2 (TGF-B2) on the proliferation and natural killer activity of decidual CD-16 CD56 bright natural killer cells.

 Cell Immunol. 1993;152:605-613.

4. CHOUB S, WELTE K, MERTELSMANN R, DUPONT B.

Prostaglandin E2 acts at two distinct pathways of T-lymphocyte activation: inhibition of Interleukin-2 production and down-regulation of transferring receptor expression.

 T. Immunol. 1985;135(2):1172-1179.

5. DEMERS L M, GABBE S G, VILLEE C A, GREEP R O.

Human chorionic gonadotrophin mediated glycogenolysis in human placental villi: A role of prostaglandins.

 Biochem Biophys Acta. 1973;313:202-210.

6. SATOH K, RYAN K J.

 Adenyl cyclase in the human placenta.

 Biochem Biophys Acta. 1971;244:618-624.

7. CORCORAN M L, KIBBEY M C, KLEINMAN H K, WAHL L M.

Laminin sikvav peptide induction of monocyte/macrophage Prostaglandin E2 and matrix metalloproteinases.

 J. Biol Chem. 1995;270(18):10365-10368.

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85%

85% of pregnant women have two episodes of nausea per day.

30%

30% of pregnant women in paid employment need time off work due to NVP.

70-80%

Nausea & vomiting in pregnancy (NVP) is very common, on average it affects 70-80% of pregnant women to a greater or lesser extent.

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