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Lee Y.S.,Fels Institute for Cancer Research and Molecular Biology | Vandevoort C.A.,California National Primate Research Center | Vandevoort C.A.,University of California at Davis | Gaughan J.P.,Temple University | And 4 more authors.
American Journal of Physiology - Endocrinology and Metabolism | Year: 2011

The elaboration of a quality oocyte is integrally linked to the correct developmental progression of cumulus cell phenotype. In humans and nonhuman primates, oocyte quality is diminished with in vitro maturation. To determine the changes in gene expression in rhesus monkey cumulus cells (CC) that occur during the final day prior to oocyte maturation and how these changes differ between in vitro (IVM) and in vivo maturation (VVM), we completed a detailed comparison of transcriptomes using the Affymetrix gene array. We observed a large number of genes differing in expression when comparing IVM-CC and VVM-CC directly but a much larger number of differences when comparing the transitions from the prematuration to the post-IVM and post-VVM states. We observed a truncation or delay in the normal pattern of gene regulation but also remarkable compensatory changes in gene expression during IVM. Among the genes affected by IVM are those that contribute to productive cell-cell interactions between cumulus cell and oocyte and between cumulus cells. Numerous genes involved in lipid metabolism are incorrectly regulated during IVM, and the synthesis of sex hormones appears not to be suppressed during IVM. We identified a panel of 24 marker genes, the expression of which should provide the foundation for understanding how IVM can be improved for monitoring IVM conditions and for diagnosing oocyte quality. © 2011 by the American Physiological Society.

Brogan R.S.,Loyola College in Maryland | Mix S.,Loyola College in Maryland | Puttabyatappa M.,University of Maryland Baltimore County | VandeVoort C.A.,California National Primate Research Center | Chaffin C.L.,University of Maryland Baltimore County
Fertility and Sterility | Year: 2010

Objective: To determine intrafollicular hormone levels and characterize the mRNA expression of the insulin-like growth factor (IGF) receptors, IGF binding proteins (IGFBP), and pregnancy-associated plasma protein-A (PAPP-A) in granulosa cells before and after an ovulatory hCG stimulus. Design: Experimental animal study. Setting: Academic medical center. Animal(s): Adult rhesus macaques. Intervention(s): Animals received exogenous FSH to promote the development of multiple preovulatory follicles. Follicles were aspirated before (0 hours) or 3, 6, 12, or 24 hours after an ovulatory hCG bolus. Main Outcome Measure(s): IGF1, IGF2, and insulin levels in follicular fluid were determined by radioimmunoassay. Messenger RNA (mRNA) levels in granulosa cells were determined by real-time reverse transcriptase-polymerase chain reaction. IGFBPs and PAPP-A in follicular fluid were determined by Western blot analysis and enzyme-linked immunosorbent assay. Result(s): IGF1, IGF2, and insulin in follicular fluid did not change during luteinization. IGF1R, IGFBP1, and IGFBP2 mRNAs were unchanged by hCG. IGF2R, IGFBP3, -5, and -6 and PAPP-A mRNA levels increased after hCG administration, while insulin receptor and IGFBP4 mRNA levels decreased after hCG administration. IGFBP3 and -6 and PAPP-A protein increased after hCG administration. Conclusion(s): Dynamic changes in the expression of the IGFBPs and PAPP-A suggest tight regulation of IGF action during ovulation and corpus luteum formation. © 2010 American Society for Reproductive Medicine.

Bales K.L.,University of California at Davis | Bales K.L.,California National Primate Research Center | Saltzman W.,University of California at Riverside
Hormones and Behavior | Year: 2016

This article is part of a Special Issue "Parental Care". Paternal care, though rare among mammals, is routinely displayed by several species of rodents. Here we review the neuroanatomical and hormonal bases of paternal behavior, as well as the behavioral and neuroendocrine consequences of paternal behavior for offspring. Fathering behavior is subserved by many of the same neural substrates which are also involved in maternal behavior (for example, the medial preoptic area of the hypothalamus). While gonadal hormones such as testosterone, estrogen, and progesterone, as well as hypothalamic neuropeptides such as oxytocin and vasopressin, and the pituitary hormone prolactin, are implicated in the activation of paternal behavior, there are significant gaps in our knowledge of their actions, as well as pronounced differences between species. Removal of the father in biparental species has long-lasting effects on behavior, as well as on these same neuroendocrine systems, in offspring. Finally, individual differences in paternal behavior can have similarly long-lasting, if more subtle, effects on offspring behavior. Future studies should examine similar outcome measures in multiple species, including both biparental species and closely related uniparental species. Careful phylogenetic analyses of the neuroendocrine systems presumably important to male parenting, as well as their patterns of gene expression, will also be important in establishing the next generation of hypotheses regarding the regulation of male parenting behavior. © 2015 Elsevier Inc.

Maninger N.,University of California at San Francisco | Maninger N.,California National Primate Research Center | Capitanio J.P.,California National Primate Research Center | Mason W.A.,California National Primate Research Center | And 2 more authors.
Psychoneuroendocrinology | Year: 2010

Most studies on the stress-responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis have focused on glucocorticoids, while few studies have investigated the adrenal secretion of dehydroepiandrosterone sulfate (DHEAS), which is unique to primates. Monkeys were chair-restrained for 2. h per day for seven consecutive days, and blood samples were collected upon placement in the chair, and at 15, 30, 60 and 120. min later. Like cortisol, DHEAS concentrations increased throughout the initial session of chair restraint (acute stress). Unlike the cortisol response, which decreased after repeated exposure to the stressor, the DHEAS response was sustained throughout the seventh session of restraint (chronic stress) and response to the seventh session of restraint did not differ from the DHEAS response to the initial session. Like cortisol, DHEAS concentrations showed a diurnal rhythm with higher concentrations in the morning compared to the evening and a decrease in response to dexamethasone (DEX) administration. After repeated exposure to the stressor, the suppression of DHEAS in response to dexamethasone was more complete, suggesting an increase in negative feedback sensitivity. These data show that DHEAS concentrations increase in response to both acute and chronic (repeated) stress and provide another measure of HPA activity that parallels cortisol during acute responses to stress but diverges in chronic or repeated stress. © 2010.

Baxter M.G.,Mount Sinai School of Medicine | Roberts M.T.,California National Primate Research Center | Gee N.A.,California National Primate Research Center | Gee N.A.,University of California at Davis | And 4 more authors.
Neurobiology of Aging | Year: 2013

Preclinical studies in aged, surgically-menopausal rhesus monkeys have revealed powerful benefits of intermittent estrogen injections on prefrontal cortex-dependent working memory, together with corresponding effects on dendritic spine morphology in the prefrontal cortex. This contrasts with the inconsistent effects of hormone therapy (HT) reported in clinical studies in women. Factors contributing to this discrepancy could include differences in the formulation and sequence of HT regimens, resulting in different neurobiological outcomes. The current study evaluated, in aging surgically menopausal rhesus monkeys, the cognitive effects of 4 HT regimens modeled directly on human clinical practice, including continuous estrogen treatment opposed by progesterone. None of the regimens tested produced any cognitive effect, despite yielding physiologically relevant serum hormone levels, as intended. These findings have implications for the design of regimens that might optimize the benefits of hormone treatment for healthy aging, and suggest that common HT protocols used by women may fail to result in substantial cognitive benefit, at least via direct effects on the prefrontal cortex. © 2013 Elsevier Inc.

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