Glucocorticoid receptor activation following elevated oocyte cortisol content is associated with zygote activation, early embryo cell division, and IGF system gene responses in rainbow trout

Abstract

Increased in ovo cortisol content of rainbow trout oocytes from w3 . 5 to w5 . 0 ng.oocyte K1 before fertilization enhances the growth of embryos and juveniles and changes the long-term expression pattern of IGF-related genes. This study used embryos reared from oocytes enriched with cortisol and the glucocorticoid receptor (GR) antagonist, RU486, to determine whether the growth-promoting actions of cortisol involve GR protein activation and modulation of gr expression. Whole-mount in situ immunohistofluorescence studies of zygotes showed that enhanced oocyte cortisol increased the immunofluorescent GR signal and activated the relocation of GR from a general distribution throughout the cytoplasm to an accumulation in the perinuclear cytoplasm. In ovo cortisol treatment increased the number of embryonic cells within 48-h post-fertilization, and RU486 partially suppressed this cortisol stimulation of cell duplication. In addition, there was complex interplay between the expression of gr and igf system-related genes spatiotemporally in the different treatment groups, suggesting a role for GR in the regulation of the expression of development. Taken together, these findings indicate an essential role for GR in the regulation of epigenomic events in very early embryos that promoted the long-term growth effects of the embryos and juvenile fish. Moreover, the pretreatment of the oocyte with RU486 had a significant suppressive effect on the maternal mRNA transcript number of gr and igf system-related genes in oocytes and very early stage embryos, suggesting an action of antagonist on the stability of the maternal transcriptome.

Cortisol treatment of prespawning female cod affects cytogenesis related factors in eggs and embryos

“…Another possibility is that the receptor activity is controlled by cofactors like the ipo7 transcript, which encodes a protein essential for the transport of the glucocorticoid receptor into the nucleus, where cortisol exerts its functions. Interestingly, it was recently observed that elevated cortisol content in rainbow trout oocytes activates the glucocorticoid receptor, leading to increased cell division in early blastula (Li et al, 2012b), which further supports our finding that elevated cortisol increases the expression of ipo7 and also affects many cytogenesis related factors. It is known that individual fish might be high and low responders to stress (Fevolden et al, 1991;Fevolden et al, 2002;Fevolden et al, 2003).…”

“…In agreement with this finding, extracellular region was also overrepresented among differentially expressed genes in liver of rainbow trout subjected to long term confinement stress (Cairns et al, 2008). Also Li et al (2012b) recently showed that cell division is increased in rainbow trout eggs containing elevated levels of cortisol. Some of the overrepresented biological processes identified in this study have previously been related to stress, and wound healing and likewise several of these were also found to be affected in salmon skin by cortisol implants (Krasnov et al, 2012).…”

“…Potential effects may also be masked by the considerable variation in these data, often observed in marine fish species (Brooks et al, 1997). However, it was recently shown that elevated levels of cortisol increase cell division in rainbow trout resulting in significantly more cells at early blastula stages (Li et al, 2012b). Unfortunately, we were not able to count cells in cod embryos at a comparable stage, however gene expression data point at increased cytogenesis during maternal stages.…”

“…The increase in cytogenesis related factors in cod eggs/embryos in response to elevated cortisol could possibly increase growth rates of embryos. We did not measure growth rates in the embryos, however earlier studies in rainbow trout (Li et al, , 2012b have reported increased embryo and juvenile growth rates in response to increased cortisol. This could explain why we saw changes in gene expression but not in phenotype at the stages measured, as increased cell division may not affect the parameters measured.…”

Programming of the hypothalamic-pituitary-interrenal axis by maternal social status in zebrafish (Danio rerio)

“…Maternal cortisol plays an important organizational role during early development in fish, and cortisol treatment of eggs or embryos alters both physiology and behaviour of the developing young (e.g. Sloman, 2010;Burton et al, 2011;Li et al, 2012;Nesan and Vijayan, 2012;Colson et al, 2015;. However, programming of offspring is probably more complex than the action of cortisol alone, because previous studies have found effects of maternal stress even in the absence of increased embryo cortisol levels -for example, on egg size in Neolamprologus pulcher (Mileva et al, 2011) and on swim performance in Oncorhynchus nerka (Sopinka et al, 2014).…”