FEMALES OF MOST MAMMALIAN SPECIES, INCLUDING HUMANS, EXPERIENCE REPRODUCTIVE DECLINE WITH AGE, ENDING IN COMPLETE LOSS OF FERTILITY BY MID-LIFE, EVEN THOUGH THERE ARE STILL PRIMARY OOCYTES WITHIN THE OVARY. CONDUCTING STUDIES ON HUMAN OOCYTES AND EMBRYOS CLEARLY HAS DRAWBACKS, INCLUDING LIMITED AVAILABILITY AND ETHICAL CONSTRAINTS ON EXPERIMENTAL MANIPULATION OF HUMAN EMBRYOS. RODENT MODELS CIRCUMVENT THE SUPPLY AND ETHICAL PROBLEMS, BUT SIGNIFICANT SPECIES DIFFERENCES IN THE LOCUS OF REPRODUCTIVE AGING EXISTS. INDEED, OVUM TRANSFER EXPERIMENTS IN MICE DEMONSTRATE THAT OOCYTES REMAIN HIGHLY FERTILE RIGHT UP TO THE AGE OF PERSISTENT DIESTRUS, WHEN THE OVARY IS EXHAUSTED OF ALL OOCYTES. EXPERIMENTS PROPOSED CAPITALIZE ON THIS INHERENT ~REPRODUCTIVE YOUTHFULNESS~ OF MOUSE OVA BY EMPLOYING THEM AS SUBSTRATES ON WHICH TO INDUCE REACTIVE OXYGEN SPECIES, ROS, AND MITOCHONDRIAL DYSFUNCTION. SINCE THE VIBRATING PROBE PROVIDES INFORMATION ON A CELL~S PHYSIOLOGY WITHOUT DISTURBING THE CELL ITSELF, IT HOLDS PROMISE FOR THE STUDY OF FEMALE REPRODUCTIVE SENESCENCE. BECAUSE CALCIUM AND PH BOTH DEPEND ON EMBRYO METABOLISM, MEASUREMENT OF CALCIUM AND PROTON FLUX SHOULD PROVIDE A NON-INVASIVE INDEX OF EMBYO DEVELOPMENT POTENTIAL. THIS PROJECT HAS ALREADY PROGRESSED SIGNIFICANTLY OVER THE PAST YEAR (SEE HIGHLIGHTS). WE PROPOSE THAT THE PROBE TECHNIQUE WILL INCREASE OUR BASIC UNDERSTANDING OF HUMAN IMPLANTATION VIABILITY AND MAY LEAD TO CLINICAL TESTS.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
3P41RR001395-14S1
Application #
5223346
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1996
Total Cost
Indirect Cost
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