Determining the role of circadian synchrony between the mother and fetus in birth outcomes

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Each year, roughly 15 million infants are born premature and at risk for dire short- and long-term health problems. Despite the extensive research that has focused on combating prematurity, we do not have a thorough understanding of the processes that regulate gestation length. One area of recent interest has focused on how disruptions of circadian rhythms affect reproductive outcomes. One example is women who undergo rotating shift work or work the night shift during pregnancy, as they have a higher incidence of preterm birth as well as other reproductive complications, such as preeclampsia and intrauterine growth restriction. However, little is known about the role of circadian rhythms in the timing of birth and which tissues may be most important in this process. We recently found that both maternal and fetal tissues exhibit daily rhythms that reliably change during pregnancy and that different circadian mutant genotypes alter birth timing. Our work, in mice, seeks to test the fundamental hypothesis that maternal-fetal coordination of circadian rhythms in physiology determines gestation length and the time of day of delivery. To test this hypothesis, this proposal will combine novel computational methods with two-color, real-time imaging of in utero gene expression simultaneously in the mother and their fetuses to determine how and when maternal and fetal circadian rhythms synchronize (aim 1). Furthermore, we will utilize our ability to perform embryo transfers and to manipulate circadian genes in specific cell types to determine the relative contributions of the fetus and maternal tissues to the timing of birth (aim 2). Completion of these aims will determine the role of maternal-fetal circadian communication in the timing of birth. These findings could help us understand how chronodisruption during pregnancy can lead to reproductive complications and identify potential therapeutic targets to prevent preterm birth.