Reproductive Sciences Unit

The Reproductive Sciences Unit provides services, training, consulting, and collaborative expertise for the study of human biology and disease in monkeys from embryonic and fetal development through puberty and reproductive senescence. Monkeys are a uniquely suitable model for these studies because they have a menstrual cycle and hormonal patterns comparable to those that occur in humans, and similar spatial and temporal patterns of organ development, placental formation, and hematopoietic and immune ontogeny.

Studies in the Reproductive Sciences Unit range from reproductive toxicology, gamete biology, and aging to the study of fetal congenital illnesses and cell and gene-based therapies. Investigators incorporate the monkey model for translational research applications which include:

• A research team that has used dioxin as a model compound to develop biomarker assays for studies with monkeys or humans, emphasizing the translational nature of this work. Studies also focus on ovarian toxicity, reproductive tract and embryonic abnormalities, and early pregnancy loss.
• Studies in collaboration with investigators in the Brain, Mind and Behavior Unit which focus on the effect of environmental estrogens on female reproductive function, and have previously shown the usefulness of this model for identifying anatomical and endocrine changes initiated during puberty.
• The development of biomarkers to monitor the hypothalamic-pituitary-ovarian axis which are used to investigate the endocrine changes associated with the menopausal transition in women and nonhuman primates; studies have demonstrated that older female macaques experience the same endocrine changes in their third decade of life that women experience in their sixth decade of life. Studies on the role of the adrenal gland in the menopausal transition are focused on identifying the endocrine basis of healthy aging in women, whereas studies in collaboration with investigators in the Brain, Mind and Behavior Unit focus on the effect of estrogen replacement on behavior and cognition.
• New contraceptive strategies including contraceptive vaccines that are intended for human use, some of which block implantation and others sperm production.
• An ovarian cell culture model which is used to study ovarian function, the role of different hormones during the peri-implantation phase of early pregnancy, and the effects of environmental toxins. Another in vitro model is used to study gene expression during the earliest stages of luteinization; these in vitro model systems provide examples of the CNPRC commitment to the 3Rs.
• In vivo techniques for the successful recovery of mature and immature oocytes that are used to develop methods for in vitro maturation and cryopreservation of primate oocytes. Services in Assisted Reproductive Technologies include semen cryopreservation, controlled ovarian stimulation, follicle aspiration, in vitro fertilization, embryo culture, and embryo freezing.
• Building on studies performed on in utero hematopoietic stem cell transplantation, where new techniques with other stem cells such as mesenchymal stem cells, endothelial progenitor cells, and embryonic stem cells focus on directed differentiation strategies and tissue regeneration and repair.
• An NHLBI-supported Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases which has the dual function of conducting research on crucial questions in cell and gene-based therapies in nonhuman primates and in providing extensive outreach and support to NHLBI-funded investigators.
• Fetal gene therapy studies that focus on the optimal gestational age(s) to perform gene transfer, the safety and efficiency of direct intraorgan routes of administration, the potential effects of gene transfer on prenatal and postnatal development, and the possible risks for the mother. Intrapulmonary studies conducted in collaboration with the Respiratory Diseases Unit suggest that direct in utero organ-targeting will most likely be the best means for obtaining maximum therapeutic effect for the treatment of prenatal disease.
• One of two NIH-suported Center of Excellence in Translational Human Stem Cell Research where studies focus on the advancement of cellular therapies for the treatment of childhood diseases.
• Studies on fetal:maternal microchimerism which can elucidate a myriad of unanswered questions in humans, such as the origin of the cells, the study of the relationship between cellular and cell-free DNA transfer between fetus and mother, and the role of these processes in health and disease.
• The study of obstructive renal disease, both from a pathogenesis and treatment perspective; obstructive nephropathy represents a major cause of renal failure in children. Similarly, AIDS-related studies, some of which are conducted in collaboration with the Virology and Immunology Unit, include those that focus on placental and fetal pathogenesis, and the safety and efficacy of novel pediatric cell and gene-based strategies.
• A state-of-the-art Ultrasound Imaging Program which provides service and expertise in all aspects of ultrasound imaging in macaques from reproductive applications to noninvasive ultrasound-guided procedures, and assessments of blood flow hemodynamics (fetus through adult). Imaging applications include optical imaging and microPET, another example of the commitment of the CNPRC to the 3Rs.

Staff Scientists

• Alice Tarantal, Ph.D., Unit Leader
• Bill Lasley, Ph.D.
• Catherine VandeVoort, Ph.D.