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Biology subjects

Nugent, B. M.

Publications and source records attributed to Nugent, B. M..

2 recordsLinked to original sources

Morpholino-mediated knockdown of the brain mineralocorticoid receptor affects glucocorticoid signaling and neuroplasticity in wild ocellated wrasse (Symphodus ocellatus)

Uncovering the genetic, physiological, and developmental mechanisms underlying phenotypic variation is necessary for understanding how genetic and genomic variation shape phenotypic variation and for discovering possible targets of selection. Although the neural and endocrine mechanisms underlying social behavior are evolutionarily ancient, we lack an understanding of the proximate causes and evolutionary consequences of variation in these mechanisms. Here, we examine in the natural environment the behavioral, neuromolecular, and fitness consequences of a morpholino-mediated knockdown of the mineralocorticoid receptor (MR) in the brain of nesting males of the ocellated wrasse, Symphodus ocellatus, a species with male alternative reproductive tactics. Even though MR knockdown did not significantly change male behavior directly, this experimental manipulation strongly altered glucocorticoid signaling and neuroplasticity in the preoptic area, the putative hippocampus homolog, and the putative basolateral amygdala homolog. We also found that individual variation in stress axis gene expression and neuroplasticity is strongly associated with variation in male behavior and fitness-related traits. The brain region-specific effects of MR knockdown on phenotypic integration in the wild reported here suggest specific neuroendocrine and neuroplasticity pathways that may be targets of selection.

animal behavior and cognition↗

Epididymal glucocorticoid receptors promote intergenerational transmission of paternal stress

Paternal preconception exposures and insults, including stress, dietary challenge and drugs of abuse, can shape offspring health and disease risk outcomes, as evidenced from retrospective human studies and more recent animal models1-16. Mechanistic examination has implicated small noncoding RNA populations in sperm, including microRNA (miRs), as carriers of paternal environmental information that consequently influence offspring development15,17-21. However, the cellular mechanisms by which these paternal signals are relayed to sperm and how they may persist remain unknown. Here, using our previously established paternal stress mouse model we identify caput epididymal epithelial glucocorticoid receptors as crucial upstream mediators of long-lasting germ cell programming. We show that glucocorticoid treatment of caput epididymal epithelial cells results in increased glucocorticoid receptor levels and enduring changes to the miR content of secreted extracellular vesicles (EVs), or epididymosomes, known to interact with sperm and alter their RNA content22,23. Further, significant changes were detected in the caput epididymal histone code long after stress ended, both in vitro and in vivo, as a potential mechanism whereby stress programmed enduring changes to EV miRs. Genetic targeting to reduce caput epididymal epithelial-specific glucocorticoid receptors reversed stress-induced chromatin remodeling and promoted cellular resilience to paternal stress, ultimately rescuing transmission of a stress dysregulated offspring phenotype. Taken together, these studies identify glucocorticoid receptor regulation of EV miRs in the caput epididymis as a key contributor in the intergenerational transmission of paternal environmental stress experiences.

neuroscience↗