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Krisher R.L.,National Foundation for Fertility Research | Prather R.S.,University of Missouri
Molecular Reproduction and Development | Year: 2012

In this essay, we propose that embryos express a metabolic phenotype necessarily different from that of differentiated somatic cells and more like that of rapidly proliferating cancer cells. This metabolic adaptation, known as the Warburg effect, supports rapid cell proliferation. One of the hallmarks of the Warburg effect is that pyruvate is directed away from the tri-carboxylic acid cycle and metabolized to lactate, resulting in a buildup of glycolytic intermediates. Although this is a comparatively inefficient way to generate ATP, this adaptation allows the cell to meet other critical metabolic requirements, including biomass production and redox regulation. Thus, utilization of WE gives proliferating cells a selective growth advantage. This model represents a completely new understanding of embryo metabolism in the context of a broad, interconnected network of metabolic mechanisms that influence viability, versus the current dogma of carbohydrate metabolism via oxidative phosphorylation. A more complete understanding of embryo metabolism is critical to better support embryo viability in vitro, and to avoid forcing embryos to adapt to suboptimal culture conditions at a significant cost to future growth and development. © 2012 Wiley Periodicals, Inc.

Krisher R.L.,National Foundation for Fertility Research
Annual Review of Animal Biosciences | Year: 2013

The oocyte is at the center of the equation that results in female fertility. Many factors influence oocyte quality, including external factors such as maternal nutrition, stress, and environmental exposures, as well as ovarian factors such as steroids, intercellular communication, antral follicle count, and follicular fluid composition. These influences are interconnected; changes in the external environment of the female translate into ovarian changes that affect the oocyte. The lengthy period during which the oocyte remains arrested in the ovary provides ample time and opportunity for environmental factors to take their toll. An appropriate environment for growth and maturation of the oocyte, in vivo and in vitro, is critical to ensure optimal oocyte quality, which determines the success of fertilization and preimplantation embryo development, and has long-term implications for implantation, fetal growth, and offspring health. © 2013 by Annual Reviews.

Yuan Y.,Urbana University | Wheeler M.B.,Urbana University | Krisher R.L.,Urbana University | Krisher R.L.,National Foundation for Fertility Research
Biology of Reproduction | Year: 2012

The objective of this study was to identify specific redoxrelated genes whose function contributes to oocyte quality and to characterize the role of redox homeostasis in oocyte development. We determined the redox genes glutaredoxin 2(GLRX2), protein disulfide isomerase family A, members 4 and 6(PDIA4, PDIA6), and thioredoxin reductase 1 (TXNRD1) were differentially expressed between adult (more competent) and prepubertal (less competent) porcine in vitro-matured (IVM) oocytes. The association between these genes and oocyte quality was further validated by comparing transcript abundance in IVM with that in in vivo-matured (VVM) prepubertal and adult oocytes. By maturing oocytes in variable redox environments, we demonstrated that a balanced redox environment is important for oocyte quality, and over-reduction of the environment is as detrimental as excess oxidation. Critical levels of reactive oxygen species (ROS) and glutathione (GSH) are required for oocyte competence. Elevated GSH and lower ROS in prepubertal oocytes suggest disrupted redox homeostasis exists in these cells. By further comparing GLRX2, PDIA4, PDIA6, and TXNRD1 expression levels in oocytes matured under thesedifferent redox environments, we found aberrant expression patterns in prepubertal oocytes but not in adult oocytes whenthe maturation medium contained high concentrations of antioxidants. These results suggest that prepubertal oocytes are less competent in regulating redox balance than adult oocytes,contributing to lower oocyte quality. In conclusion, aberrant redox gene expression patterns and disrupted redox homeostasis contribute to decreaseddevelopmental competence in prepubertal and IVM porcine oocytes. The balance between ROS and GSH plays an important role in oocyte quality. ©2012 by the Societyfor the Study of Reproduction, Inc.

Yuan Y.,University of Missouri | Krisher R.L.,University of Illinois at Urbana - Champaign | Krisher R.L.,National Foundation for Fertility Research
Methods in Molecular Biology | Year: 2012

Oocyte maturation is a critical component of in vitro embryo production. If not carried out in a precise manner under optimal conditions, subsequent fertilization and embryo development will be compromised. Here, we describe collection and in vitro maturation procedures in swine that maintain oocyte competence, resulting in successful embryo development following fertilization. These procedures can be used both for basic research purposes and large-scale production of mature oocytes for use in subsequent assisted reproductive technologies. © 2012 Springer Science+Business Media, LLC.

Krisher R.L.,National Foundation for Fertility Research | Schoolcraft W.B.,Colorado Center for Reproductive Medicine | Katz-Jaffe M.G.,National Foundation for Fertility Research
Fertility and Sterility | Year: 2015

The advent of advanced omics technologies and the application of these techniques to the analysis of extremely limited material have opened the door to the investigation of embryo physiology in a focused, in-depth approach never before possible. The application of noninvasive metabolomic and proteomic platforms to understanding embryo viability permits the characterization of individual embryos in culture. Initial clinical data have highlighted the promise of these technologies for the development of noninvasive embryo selection criteria. In this way, a complex view of embryo function can be compiled and related to embryo development, quality, and outcome. Application of knowledge gained from omics will transform both our understanding of embryo physiology as well as our ability to select viable embryos for transfer in assisted reproductive technology. © 2015 American Society for Reproductive Medicine.

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