Studies on the Effect of Prostaglandin Inhibition by Aspirin and Indomethacin on Ovulation and Pregnancy in the Rat

Author: Olufeyisipe, Adefunke Adegoke

Supervisors: Sofola O. A. and Oladapo A.

The present study was conducted with the aim of determining the effect of prostaglandin inhibition on certain aspects of the reproductive system, namely ovulation and pregnancy in young adult female Sprague Dawley rats. Prostaglandin inhibition was achieved by the administration of two widely used prostaglandin inhibitors, Aspirin and indomethacin. In order to determine the probable mechanism as well as the site of action of the prostaglandin inhibitors, the effects of human chorionic gonadotropin (HCG) and luteinizing hormone (LH) on the action of the drugs were investigated. Morphometric studies on the ovaries were also carried out. The experiments involved the testing of the effects of Aspirin and indomethacin on (i) Spontaneous ovulation (ii) Superovulation, (iii) ovulation in the presence of exogenous HCG (iv) ovulation in the presence of exogenous LH, and (v) pregnancy. The parameters measured were the preovulatory plasma LH level, the preovulatory plasma PGF level, the rate of ovulation, the pattern of follicular development in the ovary, the rate of embryo implantation, the length of gestation, and the number of offsprings delivered at the end of gestation. The result of the present study indicates that Aspirin and indomethacin when given in doses that inhibit inflammatory reactions will inhibit the process of ovulation, including follicular development and ovum maturation. In this action indomethacin was a stronger inhibitor of ovulation than aspirin. Morphometric studies reveal that while indomethacin is effective in suppressing follicular rupture, aspirin mainly retards ovum maturation. The two drugs also caused a significant reduction in plasma PGF level with indomethacin again being the more effective of the two. It therefore appears that aspirin and indomethacin may inhibit ovulation by inhibiting. Prostaglandin synthesis, implying that prostaglandins are involved in the process of ovulation. Since both aspirin and indomethacin are anti-inflammatory agents, the mechanism of prostaglandin action on ovulation may likely be an inflammatory one. It was also observed that HCG and LH did not reverse the inhibition of ovulation by aspirin and indomethacin. It is also noteworthy that the administration of aspirin indomethacin did not affect the prevalatory LH level. This indicates that aspirin and indomethacin exert their ovulation inhibitory action directly on the ovary and not on the hypothalamic axis. The results also revealed that while aspirin administration during pregnancy caused no adverse effects, indomethacin reduced the rate of implanation, prolonged the gestation period and caused the resorption of some of the fetuses. It is concluded that prostaglandins play a crucial role in the mechanisms involved in the processes of ovulation and pregnancy.