description): Studies in precocial and altricial rodents and fetal sheep provide compelling evidence that under nutrition during pregnancy resets fetal and post-natal hippocampal-hypothalamo- pituitary-adrenal (HHPAA) function. Depending on the nature and timing of prenatal challenges, HHPAA activity may increase or decrease. Some outcomes resemble the altered HHPAA activity observed in human depression and anxiety. HHPAA resetting resulting from maternal under nutrition in primate species has not been studied. This supplemental application hypothesizes that moderate maternal under nutrition (70 percent normal intake) during the final two thirds of gestation in pregnant baboons will: 1) result in fetal intrauterine growth retardation (IUGR) characterized by low fetal and placental weight, 2) increase placental 11 beta hydroxy steroid dehydrogenase (11-beta-HSD) function and CRH production, 3) increase maternal and fetal plasma cortisol and blunt fetal and maternal 24h steroid rhythms, and 4) reset fetal HHPAA function, specifically down regulate fetal glucocorticoid receptors (both CR and GR). The proposed work begins a series of studies on nutritional programming of the fetal HHPAA in nonhuman primates. They will investigate instrumented maternal and fetal baboons at 130 days gestation (dGA) and uninstrumented term fetuses. Investigators will combine state-of-the- art techniques from whole animal to gene function to examine effects of maternal under nutrition in the final two thirds of pregnancy on 1) fetal and placental growth; 2) HHPAA structure and function, especially GR; 3) placental 11-beta-HSD1 and 2 message, protein and activity; 4) in vivo alterations in M and F steroid and CRH rhythms. Their combined approach examines longitudinal time and tissue specific effects of maternal under nutrition on fetal HHPAA development. The PI and colleagues have extensive experience with all in vivo and in vitro systems required. They will use all the cores of this funded P01. This supplement addresses ideas related to their whole P01 """"""""Fetal Neuroendocrinology, Parturition and the Myometrium. The work addresses current concepts of the fetal origins of adult disease, known as the """"""""Barker Hypothesis."""""""" These studies will improve understanding of how under nutrition affects a central feature of fetal neuroendocrine development. Follow up studies will be conducted later in animals allowed to survive into adult life.
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