Effect of interleukin-1 beta on ovulation in the in vitro perfused rabbit ovary

Interleukin-1 (IL-1), a prominent 17-kilodalton member of a group of immune mediators referred to as cytokines, is secreted by a variety of immuno- and nonimmunocompetent cells. As IL-1 is an established mediator of inflammation, and ovulation may constitute an inflammatory-like reaction, consideration may be given to the possibility that IL-1 may play an intermediary role in the ovulatory process. Such a hypothesis is supported by the recent demonstration of the gonadotropin-dependent preovulatory induction of IL-1 transcripts at the level of the murine and human ovary. To date, however, the direct effect of IL-1 beta on the ovulatory process has not been examined. The objective of this study was to investigate the potential role of IL-1 beta in ovulation, oocyte maturation (nuclear and cytoplasmic), and subsequent fertilizability of in vitro ovulated oocytes. Rabbit ovaries perfused in vitro were used for these experiments. Ovarian arteries were cannulated in situ, and the ovaries were excised and perfused in vitro with or without IL-1 beta (18 ng/ml). The ovulatory efficiency of 18 ng/ml IL-1 beta-treated ovaries was 73.1%, similar to that of hCG (71.2%). Recovered oocytes were examined for their maturation and were inseminated in vitro to investigate fertilization, cleavage, and embryonic development. The fertilization rates of the 18 ng/ml IL-1 beta-treated and hCG-treated groups were 65.8% and 95.8% (P < 0.01), respectively. Cleavage rates of the IL-1 beta-treated and hCG-treated groups were 50% and 83.3% (P < 0.01), respectively. Most of the cleaved embryos from the IL-1 beta-treated group arrested at the four-cell stage, and only 2.6% of the fertilized embryos developed into the morula stage, whereas 54.2% of the hCG-treated group developed to the morula stage (P < 0.01). A cytotoxic effect of IL-1 beta is unlikely in this model. A more likely explanation is the induction of other factors by IL-1 beta, which may inhibit cytoplasmic maturation. Taken together, our findings demonstrate that in the absence of an ovulatory gonadotropic trigger, IL-1 beta can induce ovulation and oocyte maturation, facilitate fertilization, and influence subsequent embryonic development. Although fertilization and embryonic development occurred after IL-1 beta treatment, these rates were lower than those after hCG treatment. These observations give credence to the possibility that IL-1 may play an intermediary role in the ovulatory process.