Abstract

The overall goal of this study is to examine the functional significance of different mitochondrial characteristics in oocytes as markers or predictors of oocyte health, using the rhesus monkey as the most appropriate experimental model for humans. 3 approaches will be used: (i) assessment of mitochondrial localization profiles in oocytes before, during and after fertilization in vitro using multiphoton microscopy as a non-invasive analytical tool that provides 4-dimensional (4D) information; (ii) determining the functional activity of mitochondria in oocytes and embryos by measuring ATP levels at different stages of development; and (iii) evaluation of mitochondrial mutations in oocytes from humans and oocytes and embryos from young and old monkeys, as well as the evaluation of somatic mtDNA mutations in tissues and cells as a baseline marker for reproductive senescence. The study will determine the extent to which all 3 of these measures of mitochondrial characteristics are related to 1 another, and to embryo development subsequent to fertilization in vitro, in rhesus monkeys. If good correlations are found, this will indicate that the localization profiles and activity of mitochondria typical of developmentally incompetent oocytes represent a pathological condition. Thus, the """"""""normal"""""""" localization profiles could be used as a non-invasive marker or predictor of oocyte competence so that only the most viable embryos are selected for embryo transfer. This information could then be evaluated in other clinical studies for application to human oocytes and embryos. This study will also determine if mtDNA defects are manifested as disturbed mitochondrial localization profiles, altered mitochondrial activity, and/or compromised oocyte developmental competence in rhesus monkeys. Information gained in this study will also improve our understanding of the role of mitochondria in primate oocyte and embryo biology, and in the progressive loss of female reproductive capacity with age.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD045966-02
Application #
7055292
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Tasca, Richard J
Project Start
2005-04-15
Project End
2010-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
2
Fiscal Year
2006
Total Cost
$311,384
Indirect Cost

  Institution

Name
Louisiana State University-University of New Orleans
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
616680757
City
New Orleans
State
LA
Country
United States
Zip Code
70148

  Publications

Armant, D R; Fritz, R; Kilburn, B A et al. (2015) Reduced expression of the epidermal growth factor signaling system in preeclampsia. Placenta 36:270-8
Patel, Shivali; Kilburn, Brian; Imudia, Anthony et al. (2015) Estradiol Elicits Proapoptotic and Antiproliferative Effects in Human Trophoblast Cells. Biol Reprod 93:74
Dupont, Catherine; Harvey, Alexandra J; Armant, D Randall et al. (2012) Expression profiles of cohesins, shugoshins and spindle assembly checkpoint genes in rhesus macaque oocytes predict their susceptibility for aneuploidy during embryonic development. Cell Cycle 11:740-8
Leach, Richard E; Jessmon, Philip; Coutifaris, Christos et al. (2012) High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples. Hum Reprod 27:814-28
Harvey, Alexandra J; Mao, Shihong; Lalancette, Claudia et al. (2012) Transcriptional differences between rhesus embryonic stem cells generated from in vitro and in vivo derived embryos. PLoS One 7:e43239
Martínez-Hernández, M G; Baiza-Gutman, L A; Castillo-Trápala, A et al. (2011) Regulation of proteinases during mouse peri-implantation development: urokinase-type plasminogen activator expression and cross talk with matrix metalloproteinase 9. Reproduction 141:227-39
Chason, Rebecca J; Csokmay, John; Segars, James H et al. (2011) Environmental and epigenetic effects upon preimplantation embryo metabolism and development. Trends Endocrinol Metab 22:412-20
Armant, D Randall (2011) Life and death responses to trophinin-mediated adhesion during blastocyst implantation. Cell Cycle 10:574-5
Armant, D Randall (2011) Autophagy's expanding role in development: implantation is next. Endocrinology 152:1739-41
Jessmon, Philip; Kilburn, Brian A; Romero, Roberto et al. (2010) Function-specific intracellular signaling pathways downstream of heparin-binding EGF-like growth factor utilized by human trophoblasts. Biol Reprod 82:921-9

Showing the most recent 10 out of 19 publications