**8. Cyclooxygenase – COX (Prostaglandin endoperoxide synthase)**

NSAIDs1 are the most commonly used drugs for the treatment of pain for centuries. These drugs also have antipyretic and analgesic affects. They act by inhibiting the enzyme cycloox‐ ygenase (also known as Cox inhibitors). In this way, the synthesis of prostaglandins is blocked. Prostaglandins are mediators which ensure the formation of inflammation symp‐ toms as pain, fever and swelling. Arachidonic acid, which is found in cell membrane, is pre‐ cursor of prostaglandins. Prostaglandins are end products of fatty acid metabolism. With the effect of Phospholipase A2, Arachidonic acid is synthesized from membrane phospholi‐ pids. As soon as arachidonic acid is released Prostaglandin G2 and Prostaglandin H2 is syn‐ thesized by the effect of cox enzyme. Then, by means of synthase, PGD2, PGE2, PGF2, PGI2 and TxA2 are produced [41-45]. See figure 1.

**Figure 1.** Metabolism of Prostaglandins.

Nowadays, the most known NSAID is aspirin. The past of Aspirin dates back to hundreds of years. The most important step in the discovery of Aspirin is the identification of salicylic acid in 1860. Following this discovery, sodium salicylate in 1875 and phenyl salicylate in

<sup>1</sup> NSAID: Nonsteroid Anti-inflammatory Drugs

1886 were first used. But these drugs formed serious side effects in gastrointestinal system. Aspirin or acetyl salicylic acid was discovered by Felix Hoffman in 1897. It was started to be sold under the name of Aspirin by Bayer Company in 1899 [46].

For the first time, it has been identified that prostaglandin inhibitors prevent product of Cox by John Vane in 1971 [44]. Later studies have shown that Cox enzymes have different iso‐ forms and have different functions. Cox-1 is found in stomach, intestine, kidney and throm‐ bocytes, and Cox-2 is secreted in platelets, macrophages, endothelial cells [41, 47]. While classic NSAIDs inhibit both enzymes, Cox-2 inhibitors inhibit inducible Cox-2. Thanks to this, Cox-2 inhibitors can show anti-inflammatory effect without forming any side effects in gastrointestinal system and in other tissues [43]. Existence of Cox-3 enzyme was discovered by Chandrasekharan et al. in 2002 [48]. See table 1.


**Table 1.** Cox inhibitors are classified as below [41, 49]:

PGF2α occurs in response to luteal oxytocin secretion and luteolysis goes after. For this rea‐

Specific proteins (bTP-1) produced by blastocyst in cows are signals preventing luteolysis. bTP-1, inhibits the endometrium cells' oxytocin receptor production. As a result, oxytocin cannot induce PGF2α release. In addition to this, bTP-1increases protein production from uterine glands. These released proteins into uterus lumen provide nutrition of embryo [32].

are the most commonly used drugs for the treatment of pain for centuries. These

drugs also have antipyretic and analgesic affects. They act by inhibiting the enzyme cycloox‐ ygenase (also known as Cox inhibitors). In this way, the synthesis of prostaglandins is blocked. Prostaglandins are mediators which ensure the formation of inflammation symp‐ toms as pain, fever and swelling. Arachidonic acid, which is found in cell membrane, is pre‐ cursor of prostaglandins. Prostaglandins are end products of fatty acid metabolism. With the effect of Phospholipase A2, Arachidonic acid is synthesized from membrane phospholi‐ pids. As soon as arachidonic acid is released Prostaglandin G2 and Prostaglandin H2 is syn‐ thesized by the effect of cox enzyme. Then, by means of synthase, PGD2, PGE2, PGF2, PGI2

Nowadays, the most known NSAID is aspirin. The past of Aspirin dates back to hundreds of years. The most important step in the discovery of Aspirin is the identification of salicylic acid in 1860. Following this discovery, sodium salicylate in 1875 and phenyl salicylate in

son, maternal recognition of pregnancy must take place before luteolysis [32, 40].

78 Success in Artificial Insemination - Quality of Semen and Diagnostics Employed

**8. Cyclooxygenase – COX (Prostaglandin endoperoxide synthase)**

NSAIDs1

and TxA2 are produced [41-45]. See figure 1.

**Figure 1.** Metabolism of Prostaglandins.

1 NSAID: Nonsteroid Anti-inflammatory Drugs

Cox inhibitors are used with different aims in reproductive field. Among these are; blocking of ovulation and implantation, preventing post operative adhesions and hindering of pre‐ mature births (tocolytic) [50-58].

A lot of studies have been done to understand the importance of Cox enzyme in implanta‐ tion. It has been found out that COX-2 is produced by uterus luminal epithel and stroma which surround blastocyte during implantation in rats. This situation indicates that COX-2 has a fundamental role in implantation [59-60]. Again in another study, it has been identi‐ fied that female rats which have COX-1 deficiency have normal fertility and young number. Because in the presence of COX-1 enzyme deficiency, COX-2 supplies this deficit [59]. How‐ ever, female rats which have COX-2 deficiency are infertile. Because lacking of COX-2 en‐ zyme occurs ovulation, fertilization, implantation and desidualization defects [61].

Parallel with the studies done on experiment animals, studies searching the effects of NSAIDs on pregnancy rates of livestock have also been done. In these studies, flunixin me‐ glumine, meloxicam, and carprofen have been used in order to increase pregnancy rate in cows.
