This program contains three integrated projects and three well established scientific cores that continue this laboratory's testing of hypotheses fundamental to understanding fetal neuroendocrine maturation and parturition. The hypotheses are related to fetal endocrinology, placental and fetal membranes and decidual and myometrial regulation. In parallel experiments the present proposal will continue to utilize chronically instrumented pregnant sheep and non-human primates and its unique in several aspects (particularly in focussed efforts to correlate and compare work in ovine and non-human primate pregnancy). Integrated with whole animal studies will be molecular biology approaches, in vitro studies, biochemical, immunocytochemical, and endocrinological methods some of longstanding and some developed in years 06-10. The three projects use a multi-disciplinary approach in which selected single variables will be changed and results analyzed with appropriate statistical techniques. Project I continues the work conducted in Years 1-10 with on-human primates to obtain a better understanding of the integrated function of fetal and maternal neuroendocrine systems and the myometrium. It tests the overall function of prostaglandin (PG) on fetal and maternal hypothalamo- pituitary-adrenal (HPA) placental feedback and feed-forward loops. We will also investigate the role of CRH on uterine blood flow, myometrial activity and neuroendocrine function. Project II continues work performed in the previous funding period to study the integration of placental and fetal HPA axis (HPAA) function in chronically instrumented pregnant sheep. The proposed work addresses PG's role both as activators and/or stimulators of parturition at fetal and maternal hypothalamus, pituitary and adrenal as well as in placenta and uterine tissues, and the differential contribution of the two PG synthase isoforms on promotions of parturition of neuroendocrine function. Project III test the hypothesis that the fetal hippocampus plays a central role in regulating the fetal HPAA. The PI is the only investigator currently undertaking fetal stereotaxic neurosurgery in chronic whole animal investigations. We have taken note of the comments of the IRG in all projects. The specific responses are detailed within each project. Prematurity and complications of late gestation and delivery are major obstetric problems with a profound effect on perinatal mortality and morbidity. Prematurity has a disproportionate effect on, and incidence in, minority women. Our proposed experiments will define similarities and differences between sheep and non-human primates.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
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Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Ilekis, John V
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Cornell University
Other Basic Sciences
Schools of Veterinary Medicine
United States
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Kuo, Anderson H; Li, Cun; Huber, Hillary F et al. (2018) Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.). J Physiol 596:5083-5098
Spradling-Reeves, Kimberly D; Glenn, Jeremy P; Lange, Kenneth J et al. (2018) The non-human primate kidney transcriptome in fetal development. J Med Primatol 47:157-171
Huber, Hillary F; Li, Cun; Nathanielsz, Peter W (2018) 2D:4D digit ratio is not a biomarker of developmental programming in baboons (Papio hamadryas species). J Med Primatol 47:78-80
Kuo, A H; Li, J; Li, C et al. (2018) Poor perinatal growth impairs baboon aortic windkessel function. J Dev Orig Health Dis 9:137-142
Kuo, Anderson H; Li, Cun; Mattern, Vicki et al. (2018) Sex-dimorphic acceleration of pericardial, subcutaneous, and plasma lipid increase in offspring of poorly nourished baboons. Int J Obes (Lond) 42:1092-1096
Light, Lydia E O; Bartlett, Thad Q; Poyas, Annica et al. (2018) Maternal activity, anxiety, and protectiveness during moderate nutrient restriction in captive baboons (Papio sp.). J Med Primatol :
Kuo, A H; Li, J; Li, C et al. (2017) Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons. Int J Obes (Lond) 41:1299-1302
Proffitt, J Michael; Glenn, Jeremy; Cesnik, Anthony J et al. (2017) Proteomics in non-human primates: utilizing RNA-Seq data to improve protein identification by mass spectrometry in vervet monkeys. BMC Genomics 18:877
Muralimanoharan, Sribalasubashini; Li, Cun; Nakayasu, Ernesto S et al. (2017) Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction. J Mol Cell Cardiol 108:181-193
Li, Cun; Jenkins, Susan; Mattern, Vicki et al. (2017) Effect of moderate, 30 percent global maternal nutrient reduction on fetal and postnatal baboon phenotype. J Med Primatol 46:293-303

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