Because human and nonhuman primates share many unique characteristics of reproduction, especially in regard to follicle selection and function, oocyte maturation and early embryo growth, the rhesus model is especially critical for research in reproduction that can have direct applications to humans, especially in research to determine fetal origins of adult disease. This resource would be a source of oocytes and follicle cells, as well as protocols and training, for investigators that currently utilize or that want to expand their studies into a primate model to facilitate translation to human applications. Furthermore, the lack of a reliable, adequate supply of non-human primate oocytes is a major problem impeding progress in non- human primate models of early embryo development, fertilization, transgenics, embryonic stem cell lines, and production of genetically identical offspring. Improved technologies for in vitro maturation (IVM) and cryopreservation of non-human primate oocytes would help alleviate this shortage and increase the efficiency of research in this important model for human health. This resource will be developed for the purpose of providing services and samples to investigators that are outside of the Primate Centers to facilitate translational research. Use of the resource will likely encompass investigators funded by a range of categorical institutes including NICHD, NCRR, NIEHS, NIA, NIAAA. Providing access to protocols, training and, ultimately, a """"""""bank"""""""" of nonhuman primate oocytes, follicles cells, tissues and lysates is essential for the translational research bridge between other animal models and humans. Therefore, the general objectives of this project are to provide protocols and training for continually developing techniques for production of developmentally competent in vitro matured nonhuman primate oocytes and cryopreservation methods for the long-term storage of nonhuman primate oocytes. The long-term goal will be to provide a bank of oocytes and accessory cells as well as ovarian tissue and cell lysates that can be accessed by NIH funded investigators.
The specific aims of the project will be 1) Provide current protocols and training for in vitro maturation and cryopreservation of rhesus monkey oocytes;2) Develop a bank of oocytes and somatic accessory cells (cumulus and granulosa) for distribution as cryopreserved material, fixed material, and lysates for molecular analyses. Fresh oocytes and somatic accessory cells will also be available for shipment;3) Address the urgent need in both human and nonhuman reproductive biology to enhance oocyte cryopreservation and IVM methods.

Public Health Relevance

(provided by applicant): The rhesus macaque is a primate model that is highly relevant to human health. The development of resources specific for primate oocytes will be essential for moving advances in many fields beyond the mouse and toward application in humans. The development of new transgenic models of disease as well as new techniques for stem cell therapy or genetic programming will require large numbers of rhesus oocytes so that translational research efforts will be successful.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Resource-Related Research Projects (R24)
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National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Moro, Manuel H
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University of California Davis
Obstetrics & Gynecology
Schools of Medicine
United States
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Ruebel, Meghan L; Schall, Peter Z; Midic, Uros et al. (2018) Transcriptome analysis of rhesus monkey failed-to-mature oocytes: deficiencies in transcriptional regulation and cytoplasmic maturation of the oocyte mRNA population. Mol Hum Reprod 24:478-494
Midic, Uros; Goheen, Benjamin; Vincent, Kailey A et al. (2018) Changes in gene expression following long-term in vitro exposure of Macaca mulatta trophoblast stem cells to biologically relevant levels of endocrine disruptors. Reprod Toxicol 77:154-165
Midic, Uros; Vincent, Kailey A; VandeVoort, Catherine A et al. (2016) Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells. Reprod Toxicol 65:382-393
VandeVoort, Catherine A; Mtango, Namdori R; Midic, Uros et al. (2015) Disruptions in follicle cell functions in the ovaries of rhesus monkeys during summer. Physiol Genomics 47:102-12
Chaffin, Charles L; Latham, Keith E; Mtango, Namdori R et al. (2014) Dietary sugar in healthy female primates perturbs oocyte maturation and in vitro preimplantation embryo development. Endocrinology 155:2688-95
Chaffin, Charles L; Vandevoort, Catherine A (2013) Follicle growth, ovulation, and luteal formation in primates and rodents: a comparative perspective. Exp Biol Med (Maywood) 238:539-48
Chaffin, Charles L; Lee, Young S; VandeVoort, Catherine A et al. (2012) Rhesus monkey cumulus cells revert to a mural granulosa cell state after an ovulatory stimulus. Endocrinology 153:5535-45
VandeVoort, Catherine A; Hill, Dana L; Chaffin, Charles L et al. (2011) Ethanol, acetaldehyde, and estradiol affect growth and differentiation of rhesus monkey embryonic stem cells. Alcohol Clin Exp Res 35:1534-40
Duffy, Diane M; VandeVoort, Catherine A (2011) Maturation and fertilization of nonhuman primate oocytes are compromised by oral administration of a cyclooxygenase-2 inhibitor. Fertil Steril 95:1256-60
Brogan, Rebecca S; MacGibeny, Margaret; Mix, Scott et al. (2011) Dynamics of intra-follicular glucose during luteinization of macaque ovarian follicles. Mol Cell Endocrinol 332:189-95

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