UC Berkeley

‘Homeostasis’ is the physiological process of maintaining a stable equilibrium, operating within optimal limits to promote health and prevent illness. Deviations from homeostasis can have adverse consequences for one’s health. However, physiological and behavioral needs vary markedly over the course of the day, necessitating that biological systems are adjusted correspondingly. Likewise, physiological needs change over the female reproductive cycle, with ovulation, pregnancy and fetal development, and parturition requiring specifically-timed patterns of hormone secretion regulated by the circadian system. Disruption to homeostasis, either by circadian misalignment or by exposure to stress, has marked, negative consequences for female reproductive health, including ovulation, pregnancy success and maintenance, and offspring development. The overarching goal of this dissertation research is to understand the neural and hormonal mechanisms underlying reproductive health and how these mechanisms are affected by disruption to homeostasis through circadian misalignment and stress. This dissertation considers two aspects of the female reproductive cycle, the ovulatory cycle and pregnancy. Despite a significant volume of knowledge detailing the circadian regulation of ovulation and the negative impact of stress of reproductive health, the mechanisms underlying these events remain poorly understood. Chapter 2 investigates the time-dependent sensitivity of the reproductive axis to the inhibitory neuropeptide RFamide-related peptide-3 (RFRP-3) in the control of the neuroendocrine events required for ovulation. Chapters 3-5 explore how stress hormones act on the brain, ovaries, and placenta to compromise pregnancy success and fetal development. These studies inform our understanding of the complex neural and endocrine networks regulating environmental and physiological processes involved in promoting female reproductive health.