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INVESTIGATOR: Lemley, C.

PERFORMING INSTITUTION:
NORTH DAKOTA STATE UNIV
FARGO, NORTH DAKOTA 58105

ROLE OF MELATONIN DURING MID-GESTATION ON FETAL GROWTH IN SHEEP

NON-TECHNICAL SUMMARY: Mortality is increased in offspring of low birth weight, while surviving low birth weight offspring are associated with poor growth performance. Therefore, increasing fetal growth during gestation can decrease lamb mortality rates and improve offspring performance. The relationship between birth weight and offspring performance has a substantial impact on food production not only in the U.S. but other developing countries which rely heavily on sheep and goat production. The placenta is involved in transporting wastes and nutrients to the growing fetus; therefore, therapeutic supplements designed to improve blood flow to the placenta can have a direct impact on fetal growth and development. This project will examine the effect of melatonin supplementation on uterine and umbilical blood flow, both of which play an important role in supplying oxygen and nutrients to the growing fetus. We anticipate that melatonin will increase uterine and umbilical blood flow and improve fetal growth and development. In addition, we will evaluate the mechanism behind these melatonin mediated pathways, by chronically infusing pregnant sheep with a compound that blocks melatonin receptors. We anticipate that blocking melatonin receptors will result in decreased uterine and umbilical blood flow and fetal growth. The findings from this project will allow for the design and implementation of possible interventions that could be used to improve birth weights. In addition, novel research strategies could be developed to study placental and fetal development.

OBJECTIVES: The long-term goal is to determine the possible mechanisms that dietary supplements, particularly melatonin, may modify placental function and fetal development. This proposal is innovative because dietary melatonin supplementation during mid-gestation in sheep and the resultant fetal growth has not been determined. Recent evidence in nutrient restricted rats supplemented with melatonin showed an increase in birth weights compared to their respective controls. Moreover, low melatonin concentrations have been associated with an increased incidence of spontaneous abortions, which further exemplifies the need for research in this field. Interestingly, we identified melatonin receptor protein expression in the sheep placenta; however, a paucity of information exists on the role of melatonin in placental and fetal development. Therefore, the central hypothesis is that melatonin supplementation during mid-gestation will improve uteroplacental blood flow, placental efficiency and fetal growth. In addition, we believe these melatonin responses are receptor mediated. The hypothesis will be addressed through the specific objectives, which are to: Objective 1: Determine uteroplacental blood flow and fetal growth during mid-gestation in undernourished and control ewes supplemented with or without melatonin. Objective 2: Determine uteroplacental blood flow and fetal growth following chronic in vivo uterine artery infusions of vehicle, melatonin or melatonin receptor antagonist during mid-gestation. The specific outputs for the project include: conducting the animal experiments, analyzing data and disseminating research findings at national meetings and through peer-review publications. Moreover, as a USDA Fellow, the PI will seek strong research collaborations as well as assisting with the training of undergraduate and graduate students in Animal Science. Therefore, these outputs will be focused on establishing research independence and teaching credentials, which are main priorities of the Fellowship Program.