Grant: Discovery Grants Program - Individual

Anthropogenic chemicals can negatively impact fish reproduction. Successful reproduction requires completion of oogenesis, a multi-step process in which female fish produce mature, fertilizable eggs. Oogenesis begins shortly after fertilization with the formation of primordial germ cells (PGCs) that give rise to primary oocytes in response to 17a,20ß-dihydroxy-4-pregnen-3-one (17a,20ß-DP), also known as maturation inducing hormone (MIH). Oogenesis culminates with MIH activation of membrane progestin receptors (mPRs) to initiate a signaling cascade resulting in maturation of the oocyte so that it is fertilizable. Little is known about disruption of oocyte maturation as a mechanism of reproductive impairment, including species differences in sensitivity to disruption of oocyte maturation and the molecular and biochemical mechanisms by which chemicals impair oocyte maturation. In our research with zebrafish and Japanese medaka, we have observed inhibition of MIH-stimulated oocyte maturation under three unique exposure scenarios. First, when immature oocytes are acutely exposed (< 24 h) to chemical stressors, in vitro. Second, when adult fish are chronically exposed (10-21 d) to chemicals either via water or diet. Third, when fish are exposed as embryos and reared to sexual maturity in clean water. Thus, we hypothesize that mechanisms of disruption of oocyte maturation are multifaceted and vary with duration of exposure and with life-stage at exposure. The objective of the research proposed in this NSERC DG is to characterize mechanisms of chemical disruption of MIH-stimulated oocyte maturation across three fish species - zebrafish, fathead minnow, and Japanese medaka. The brominated flame retardant, TBCO, will be used as a model chemical to disrupt oocyte maturation. We will first develop an oocyte maturation assay for fathead minnows, to complement our existing assays with zebrafish and Japanese medaka. A combination of in vivo and in vitro chemical exposures, paired with molecular (mRNA and microRNA profiling), biochemical, and biophysical methods will be used to investigate mechanisms of oocyte maturation inhibition across our model species. Molecular mechanisms by which embryonic and adult exposures cause oocyte maturation inhibition will be identified and compared by use of whole transcriptome and epigenome (DNA methylation) analysis to determine reprogramming of gene expression. By examining the molecular mechanisms underlying impairment of oocyte maturation induced by exposures at various life stages and across different teleost species, this research will significantly enhance our knowledge of the intricacies of oogenesis regulation. Within the field of aquatic ecotoxicology, it will advance our understanding of endocrine disruption, and allow for the development of innovative tools that can be employed for the prediction and monitoring of these effects, thereby shaping the future of research and application in these areas.