This proposal is designed to study maternal coordination of the fetal circadian clock located in the suprachiasmatic nuclei (SCN). Experiments will be performed in rats and a small number of squirrel monkeys. Either glucose utilization of the fetal SCN, as measured by the 14C-labeled deoxyglucose method, or pineal N-acetyltransferase activity in 10-day-old pups will be used to monitor the timing of the fetal clock. Drinking behavior will be used to monitor circadian function in pregnant rats. One phase of study will examine the physiological significance of maternal coordination. First, the possibility that the entrained fetal clock initiates the cascade of events that lead to the circadian-based initiation of birth will be investigated in the rat. This will be studied by performing maternal SCN lesions at various gestational ages and examining the effects on the timing of birth. Second, artificial burrows will be used to determine whether maternal coordination confers an adaptive advantage to the pups on emergence from the burrow into the external environment. Another phase of study will investigate the mechanism by which the mother rat coordinates the timing of the fetal clock. These studies will focus on a humoral mechanism. If the timing of the fetal clock is found to be set by the mother prior to the 12th day of gestation, studies will be directed at prolactin as the signal. If the fetal timing is not set until later in gestation, then various maternal endocrine organs will be extirpated. Once the organ has been found as the source of the signal, a series of experimental approaches will be used to determine which of the various substances secreted by the organ is involved in the communication. If the above do not disrupt maternal coordination, experiments using restricted feeding schedules and a cross-transfusion method will be used to delineate whether the mechanism involves behavior. The existence of maternal-fetal coordination in primates will be investigated in pregnant squirrel monkeys using the deoxyglucose method. The results of these studies will provide new information about a novel form of communication from mother to fetus. Elucidation of the maternal mechanism will provide a powerful tool for manipulating the development and function of the SCN clock.
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