Redox Status of the Oviduct: INTRODUCTION
Because embryos are sensitive to heat stress during early development, an increase in maternal body temperature often leads to embryonic death. Such heat stress-induced early embryonic loss has been reported in a wide range of mammals and is prominent in domestic animals with enhanced metabolic rates and high productivity. In lac-tating dairy cows with high milk yields, hyperthermia caused by heat stress becomes evident at temperatures as low as 27°C, resulting in reduced fertility.
Previous studies in cattle and mice have shown that the susceptibility of preimplantation embryos to heat stress is stage-dependent (i.e., the zygote is more sensitive than the morula or blastocyst to high temperatures). Based on results using in vitro culture systems, this phenomenon has been ascribed to the stage-dependent acquisition of thermotolerance and the ability to synthesize glutathione (GSH). In cultured embryos, thermotolerance can be induced by short-term, mild heat shock at the 8-cell or morula stage but not at the zygote or 2-cell stage. However, the thermotolerance theory cannot fully explain the susceptibility of early embryos to maternal heat stress, because subsequent studies have revealed that bovine 2-cell embryos can synthesize increased heat shock protein 70 (HSP70) in response to heat shock but cannot develop thermotolerance. In addition, exposure of bovine zygotes to fluctuating high temperatures carefully mimicking the rectal temperature of heat-stressed cows that experienced early embryonic death did not compromise normal development to the blastocyst stage. Recently, we observed a similar phenomenon in mice: The deleterious effects of maternal heat stress on zygotes were not related to high body temperature alone but were mediated via physiological changes in the maternal environment that increased intracellular oxidative stress, as shown by the increased H2O2 concentrations and reduced GSH content within the embryo.
Early stage embryos are also sensitive to oxidative stress. The exposure of early embryos to oxidative stress under culture conditions disrupts normal development. When mouse zygotes are exposed to oxidative stress, development is consistently arrested at the 2-cell stage. Although the cytological mechanisms of the 2-cell block induced by oxidative stress are not completely understood, an embryo blocked at the 2-cell stage is arrested at the G2/M phase of the cell cycle. This cell block is caused by the inactivation of maturation-promoting factor (MPF) or a defect in the dephosphorylation of Cdc2, an active component of MPF and a key molecule in the cell cycle. These findings led us to speculate on the possible involvement of oxidative stress-mediated cell block in heat stress-induced early embryonic death. Therefore, the present series of experiments was designed to determine whether maternal heat stress enhances oxidative stress in the oviduct or oviduct fluid, which determines the embryo microenvironment, and whether a deficiency in developmental competence in maternally heat-stressed zygotes is correlated with a defect in Cdc2 activity at the 2cell stage.