** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** LUTEAL INSUFFICIENCY HINDERS MATERNAL RECOGNITION OF PREGNANCY AND FERTILITY IN CATTLE, BUT PROGESTERONE (P4) SUPPLEMENTATION HAS INCONSISTENT RESULTS ON FERTILITY DUE TO THE VARIABILITY OF PLASMA PROGESTERONE ACROSS INDIVIDUALS AND NON-PHYSIOLOGICAL PATTERNS INDUCED BY SUPPLEMENTATION. A PURIFIED NERVE GROWTH FACTOR- Β (NGF) BY OUR TEAM INCREASED THE RELEASE OF LH WITHOUT CHANGES IN PLASMA ESTRADIOL, FOLLOWED BY A LUTEOTROPIC EFFECT THAT MIMICS PHYSIOLOGICAL RESPONSE. THUS, IT IS REASONABLE TO SURMISE THAT NGF MAY EXERT CONCURRENT EFFECTS ON THE HYPOTHALAMUS AND OVARY THAT OPTIMIZES OVULATION AND LUTEAL DEVELOPMENT. HOWEVER, NGF EFFECTS IN THE HYPOTHALAMUS HAVE NOT BEEN EVALUATED. THERE IS, THEREFORE, A CRITICAL NEED TO ASSESS NGF EFFECTS ON GNRH RELEASE BY THE HYPOTHALAMUS CONCURRENT WITH PITUITARY AND OVARIAN RESPONSES. OUR LONG-TERM GOAL IS TO UNDERSTAND TO ROLE OF NGF IN THE HYPOTHALAMIC-OVARIAN AXIS (HPOA) TO OPTIMIZE ITS USE AS A THERAPEUTIC AND POTENTIAL GENOMIC TARGET TO IMPROVE FERTILITY IN CATTLE. OUR CENTRAL HYPOTHESIS IS THAT NGF ELICITS GNRH RELEASE THAT AUGMENTS LH RELEASE CONCURRENTLY WITH IMPROVED OVARIAN CELL PROLIFERATION AND STEROID PRODUCTION, PROMOTING LUTEAL AND CONCEPTUS DEVELOPMENT AND EARLY PREGNANCY MAINTENANCE. OUR SPECIFIC AIMS ARE:TO ASSESS NGF EFFECTS ON GNRH, NGF IN CEREBRAL SPINAL FLUID, PLASMA LH, PROGESTERONE, AND ESTRADIOL CONCENTRATIONTO DETERMINE NGF AND ITS RECEPTORS PRESENCE IN THE HPOATO CHARACTERIZE THE EFFECTS OF NGF ON THE HPOA TRANSCRIPTOMEWE WILL USE A CLASSIC MODEL OF CANULATION OF THE THIRD VENTRICLE IN BEEF HEIFERS TO ASSESS HYPOTHALAMIC AND OVARIAN TREATMENT RESPONSES, INCLUDING CONTROL/NO-GNRH ANTAGONIST, NGF/NGF/NO-GNRH ANTAGONIST, CONTROL/ACYLINE, NGF/ACYLINE. THE RATIONALE FOR THE PROPOSED RESEARCH IS THAT UNDERSTANDING THE ROLE OF NGF IN HPOA IS CRITICAL TO MODULATING NGF USE AS A THERAPEUTIC OR GENOMIC SELECTION TARGET TO OPTIMIZE FERTILITY.
$650,000FY2023National Institute of Food and AgricultureUSDA
University Of California, Davis