Project Summary
The highly conserved vertebrate G protein-coupled receptor family SREB (Super-conserved Receptors Expressed in Brain) has received research attention in the past two decades as potential therapeutic targets for human neurological diseases. Functions of individual family members, however, remain poorly understood, because endogenous ligands are not well characterized or identified. One recently identified ligand is phoenixin (PNX). PNX is produced in two small peptide forms (14 aa or 20 aa), and evidence supports SREB3 as one receptor. Recent studies in mammals and fish have identified conserved PNX roles in reproduction in the brain, and have determined it acts as an intraovarian factor promoting gonad development. In addition, our recent work on fish SREBs demonstrate that some teleosts exhibit an additional, duplicated form of SREB3 (SREB4) that is also highly expressed in the brain, but its function is unknown. Functional studies on the PNX/SREB system in fish would improve both our understanding of conserved roles for SREBs across vertebrates and may provide insight into PNX as a treatment for reproductive dysfunction as a new hormone that stimulates reproductive maturation and development. The objective of this study is to determine the effects of PNX-14 in female green-spotted puffer (Dichotomyctere nigroviridis), a species with both high SREB3/SREB4 expression and one that exhibits reproductive dysfunction in captivity. PNX-14 will be administered through intraperitoneal injection (10 or 100 ng/g body weight), and we will measure whether the hormone improves reproductive endpoints as well as fertilization success and larval survival. Hypothalamic-pituitary-gonadal (HPG) axis effects will be quantified through transcriptome sequencing analyses, qPCR, liver vitellogenin production and hormone measurements (i.e., plasma sex steroids). This research is significant as it represents the first known study in any vertebrate to use a transcriptomic approach to understand PNX effects, and could serve as a first step toward future applications of PNX as a reproductive aid. |
Significance
The proposed project will provide novel information on the effects of the PNX hormone on vertebrate reproduction as well as its potential usefulness as a spawning aid for commercial applications in fish. Through this project, undergraduate students in rural, western Maine will also gain foundational training in molecular biology and bioinformatics approaches critical to future careers in biomedical sciences.