NUCLEAR PROGESTIN RECEPTOR REGULATES FERTILITY AND SPAWNING IN FEMALE CICHLID ASTATOTILAPIA BURTONI

Abstract

Knowing when to mate and how to behave is important for maximizing reproductive fitness. In the cyclical female reproductive system, reproductive state and behaviors are synchronized through hormones. However, the mechanisms underlying this synchronization are not well understood. I utilize gene editing in the cichlid fish Astatotilapia burtoni to understand the effects of hormones on its well-documented spawning routine. In female cichlids, prostaglandin F2a (PGF2α) drives spawning behaviors. Sensitivity to PGF2α and expression of its receptor, ptgfr, varies across the reproductive cycle. I look to progestin as a potential regulator of PGF2α sensitivity. Increasing progestin levels (important in final egg maturation) precede PGF2α levels which rise during spawning. Additionally, progestin upregulates ptgfr mRNA in the preoptic area (POA) of the brain. To test whether progestin regulates prostaglandin sensitivity and reproductive behaviors, we developed a CRISPR/Cas9 progestin receptor (Pgr) mutant. Pgr-mutant females are infertile with large ovaries and reduced spawning behaviors. I find that pgr regulates fertility by controlling ovulation similar to past Pgr knockout models (Chapter 2). I devised a radio frequency identification (RFID) and video monitoring system to comprehensively document the natural spawning behaviors of females, and find that Pgr is necessary for a natural circling response (Chapter 3). Finally, I demonstrate successful rescue of spawning behavior in the absence of a functional progestin receptor (Chapter 4). Taken together, these results suggest that the PGF2α-sexual behavior circuit is intact in the absence of Pgr signaling despite Pgr being necessary for progestin-induced ptgfr mRNA upregulation. Overall, this study advances our understanding of how endocrine and neuromodulatory pathways integrate to maximize reproductive fitness.