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The role of RFRP-3 in chronic stress induced reproductive dysfunction and astrocyte communication

Abstract

Though it is well established that chronic stress induces female reproductive dysfunction, whether stress negatively impacts fertility and fecundity when applied prior to mating and pregnancy has not been well explored. My dissertation has investigated the mechanism behind stress-induced infertility in female rodents, as well as the long-term effects of chronic stress on reproductive success. Using naturally cycling female rats, Chapter 2 looks at changes in reproductive hormones and behavior after chronic immobilization stress. I also examined the long-term repercussions of chronic stress, allowing animals recovery from the stressors and looking at later mating and pregnancy success. My research has focused primarily on the role of a reproductive inhibitory hormone, RFRP-3, a hypothalamic peptide modulated by high stress. However, in Chapter 3, I investigate a new mechanism for RFRP-3 outside of that role, in hippocampal astrocytes. I see that RFRP-3 may also mediate an effect on how astrocytes connect and communicate with each other within the hippocampus. This opens a new intriguing line of research for novel roles of RFRP-3 outside of reproduction. These studies show that chronic stress has long-term effects on pregnancy success, even post-stressor, that are mediated by RFRP3, and point to RFRP3 as a potential clinically-relevant single target for stress-induced infertility.

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