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BEEF CATTLE ARE A MAJOR ECONOMICAL COMMODITY IN THE UNITED STATES AND A GOOD WAY TO STUDY HUMAN OVARIAN FUNCTION. THE CORPUS LUTEUM (CL) IS A STRUCTURE THAT DEVELOPS FROM THE REMAINING CELLS AFTER OVULATION OF THE OOCYTE. ITS PRIMARY FUNCTION IS TO PRODUCE PROGESTERONE, A KEY HORMONE TO MAINTAIN NORMAL REPRODUCTIVE CYCLES AND SUPPORT PREGNANCY. WHAT KEEPS THE CL FUNCTIONING IS AN IMPORTANT AREA OF RESEARCH TO STUDY, AS CL FAILURE CAN CAUSE LOW PROGESTERONE, WHICH MAY AFFECT THE FEMALE'S HEALTH OR REDUCE PREGNANCY SUCCESS. PRELIMINARY DATA HAS SUGGESTED THAT THE LUTEAL CELLS OF A MATURE, HEALTHY CL HAVE SIMILAR FEATURES AS CELLS THAT HAVE BECOME SENESCENT, A STATE IN WHICH CELLS REACH THE END OF THEIR REPLICATION CAPABILITIES BUT CAN STILL FUNCTION. A CELL MAY BE SENESCENT AS A RESULT OF DISEASE, DNA DAMAGE, OR SIMPLY REACHING THEIR MAXIMUM NUMBER OF DIVISIONS. LIKE SENESCENT CELLS, LUTEAL CELLS DO STOP DIVIDING, THEY HAVE A SIMILAR EXPRESSION PROFILE FOR GENES ASSOCIATED WITH SENESCENCE, AND THEIR METABOLISM SHIFTS SIGNIFICANTLY. FIRST, WE WILL TRACK THE INDUCTION OF SENESCENCE IN THE CELLS LEADING UP TO THE FORMATION OF A MATURE CL IN THE BEEF COW ACROSS SEVERAL OVARIAN STAGES. NEXT, WE WILL COLLECT GRANULOSA AND THECA CELLS FROM ANTRAL FOLLICLES AND MIMIC THE LUTEINIZATION PROCESS TO LOOK MORE CLOSELY AT HOW SENESCENCE MAY BE INVOLVED IN THE TRANSITION FROM A FOLLICULAR TO A LUTEAL CELL. FINALLY, WE WILL TREAT CELLS FROM A MATURE CL FROM THE MIDDLE OF THE LUTEAL PHASE WITH DRUGS TYPICALLY USED TO TREAT SENESCENT RELATED DISEASES TO INVESTIGATE HOW SENESCENCE MAY HAVE ROLES IN CL FUNCTION AND LIFESPAN. THE FINDINGS FROM THESE STUDIES WILL PROVIDE NEW INSIGHTS INTO HOW THE CL FUNCTIONS AND MAINTAINS ITSELF DURING THE ESTROUS CYCLE. THIS WILL ALSO SET THE GROUNDWORK FOR FUTURE STUDIES TO DETERMINE HOW WE CAN UTILIZE THE SENESCENT PHENOTYPE TO DEVELOP INTERVENTIONS AND THERAPIES TO IMPROVE LUTEAL FUNCTION BEFORE AND DURING PREGNANCY.

$225,000FY2025National Institute of Food and AgricultureUSDA

Board Of Regents Of The University Of Nebraska

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BEEF CATTLE ARE A MAJOR ECONOMICAL COMMODITY IN THE UNITED STATES AND A GOOD WAY TO STUDY HUMAN OVARIAN FUNCTION. THE CORPUS LUTEUM (CL) IS A STRUCTURE THAT DEVELOPS FROM THE REMAINING CELLS AFTER OVULATION OF THE OOCYTE. ITS PRIMARY FUNCTION IS TO PRODUCE PROGESTERONE, A KEY HORMONE TO MAINTAIN NORMAL REPRODUCTIVE CYCLES AND SUPPORT PREGNANCY. WHAT KEEPS THE CL FUNCTIONING IS AN IMPORTANT AREA OF RESEARCH TO STUDY, AS CL FAILURE CAN CAUSE LOW PROGESTERONE, WHICH MAY AFFECT THE FEMALE'S HEALTH OR REDUCE PREGNANCY SUCCESS. PRELIMINARY DATA HAS SUGGESTED THAT THE LUTEAL CELLS OF A MATURE, HEALTHY CL HAVE SIMILAR FEATURES AS CELLS THAT HAVE BECOME SENESCENT, A STATE IN WHICH CELLS REACH THE END OF THEIR REPLICATION CAPABILITIES BUT CAN STILL FUNCTION. A CELL MAY BE SENESCENT AS A RESULT OF DISEASE, DNA DAMAGE, OR SIMPLY REACHING THEIR MAXIMUM NUMBER OF DIVISIONS. LIKE SENESCENT CELLS, LUTEAL CELLS DO STOP DIVIDING, THEY HAVE A SIMILAR EXPRESSION PROFILE FOR GENES ASSOCIATED WITH SENESCENCE, AND THEIR METABOLISM SHIFTS SIGNIFICANTLY. FIRST, WE WILL TRACK THE INDUCTION OF SENESCENCE IN THE CELLS LEADING UP TO THE FORMATION OF A MATURE CL IN THE BEEF COW ACROSS SEVERAL OVARIAN STAGES. NEXT, WE WILL COLLECT GRANULOSA AND THECA CELLS FROM ANTRAL FOLLICLES AND MIMIC THE LUTEINIZATION PROCESS TO LOOK MORE CLOSELY AT HOW SENESCENCE MAY BE INVOLVED IN THE TRANSITION FROM A FOLLICULAR TO A LUTEAL CELL. FINALLY, WE WILL TREAT CELLS FROM A MATURE CL FROM THE MIDDLE OF THE LUTEAL PHASE WITH DRUGS TYPICALLY USED TO TREAT SENESCENT RELATED DISEASES TO INVESTIGATE HOW SENESCENCE MAY HAVE ROLES IN CL FUNCTION AND LIFESPAN. THE FINDINGS FROM THESE STUDIES WILL PROVIDE NEW INSIGHTS INTO HOW THE CL FUNCTIONS AND MAINTAINS ITSELF DURING THE ESTROUS CYCLE. THIS WILL ALSO SET THE GROUNDWORK FOR FUTURE STUDIES TO DETERMINE HOW WE CAN UTILIZE THE SENESCENT PHENOTYPE TO DEVELOP INTERVENTIONS AND THERAPIES TO IMPROVE LUTEAL FUNCTION BEFORE AND DURING PREGNANCY. · GrantIndex