Justin Nelson L&S Sciences
Investigating the Mechanisms Governing Kisspeptin Cell Activity in Reproduction
Fertility in women and across mammalian species requires a series of temporally coordinated neuroendocrine events by the circadian system in the brain. Disruptions to circadian timing across mammalian species from stress or environmental factors result in irregularities in the estrous/menstrual cycles, reduced fertility, and increased miscarriage rates. The proposed studies examine the role of neuroendocrine signaling events and circadian timekeeping in ovulation. Across mammalian species, ovulation requires timed neuroendocrine events organized by the master circadian pacemaker in the suprachiasmatic nucleus (SCN). Evidence points to E2-sensitive kisspeptin (Kp) neurons, potent stimulators of the reproductive axis that maintain their own circadian timekeeping, as the locus for estradiol (E2) and neuroendocrine signal integration. The preovulatory luteinizing hormone (LH) surge, the hormone signaling cascade required for ovulation, is triggered by timed neuroendocrine signals from the SCN to kisspeptin (Kp) neurons. Alterations in neuroendocrine signals to Kp neurons results in disrupted fertility. Findings from the proposed studies have the potential to identify therapeutic targets for treating infertility and to maximize female reproductive health in the face of circadian disruption.
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