Effect of actinomycin D on luteal regression induced by intrauterine devices.

Abstract

Six experiments using a total of 74 ewes were conducted to investigate the effects of a single intrauterine injection of actinomycin D at day 2 of the estrous cycle on regression of corpora lutea (CL) induced by intrauterine devices (IUD's). Intrauterine devices inserted on day 2 caused regression of CL by day 8. Intrauterine administration of 500 µg or 250 µg of actinomycin D blocked the luteolytic effect of IUD's. However, when administered alone, actinomycin D reduced the mean weight of CL. Additional experiments confirmed the observation that a single intrauterine injection of actinomycin D on day 2 caused regression of CL in a proportion of the treated ewes. Either actinomycin D or IUD's reduced the mean weight of CL at day 8, but the combination of the two treatments produced little if any reduction. Ewes with one CL on each ovary were treated bilaterally with IUD's and unilaterally with 250 µg or 50 µg of actinomycin D. In both experiments the weights of CL were greater (P<.01) on the side of actinomycin D treatment. These experiments demonstrate the ability of intrauterine administration of actinomycin D to block the luteolytic effects of an IUD. However, actinomycin D alone had other effects which by themselves were detrimental to the CL. The functional life of the corpus luteum (CL) is subject to experimental modification. When intrauterine devices (IUD's) were inserted at some time during the first 3 days after estrus in the ewe, the development of the CL was inhibited and the length of the estrous cycle shortened (Moore and Nalbandov, 1953; Inskeep et al., 1962; Ginther, Pope and Casida, 1966). Uterine inflammation induced early in the cycle by injections of chemicals or suspensions of bacteria caused premature regression of CL (Brinsfield and Hawk-, 1968; Woody, Ginther and Pope, 1969). Insertion of IUD's in ewes on day 2 of the estrous cycle increased endometrial prostaglandin FZ 0 ,,concentration significantly at day 5 (Wilson et al., 1972). Spilman and Duby (1972) found the endometrial concentration of prostaglandins of the F-series to be greatest in the immediate vicinity of the IUD and that the increased endometrial concentration was accompanied by an increase in uterine venous prostaglandin levels. Subcutaneous injections of the anti-inflammatory drug, indomethacin, blocked the increase in prostaglandin F caused by the insertion of an IUD and prevented IUD-induced luteal regression (Spilman and Duby, 1972). The mechanisms by which IUD's cause the uterus to produce a luteolytic effect are not understood. Intrauterine application of actinomycin D on day 11 of the estrous cycle delayed cyclic CL regression and prevented the luteolytic effects of exogenous estradiol (French and Casida, 1973). These observations led to the hypothesis that the synthesis of a uterine luteolytic substance at the end of the estrous cycle is dependent on induction of RNA synthesis. If the luteolytic effect of an IUD requires DNA-dependent RNA synthesis then IUD-induced luteolysis should be blocked by actinomycin D.