Transcriptional signature of progesterone in the fathead minnow ovary (Pimephales promelas)

Abstract

A growing number of studies have examined transcriptional responses to sex steroids along the hypothalamic-pituitary-gonadal axis in teleost fishes. However, data are lacking on the molecular cascades that underlie progesterone signaling. The objective of this study was to characterize the transcriptional response in the ovary of fathead minnows (Pimephales promelas) in response to progesterone (P4) using transcriptomics. Fathead minnow ovaries were exposed in vitro to 500 ng P4/L. Germinal vesicle migration and breakdown (GVBD) was observed and microarrays were used to identify gene cascades affected by P4. Microarray analysis identified 1,702 differentially expressed transcripts after P4 treatment. Functional enrichment analysis revealed that transcripts involved in the molecular functions of protein serine/threonine kinase activity, ATP binding, and activity of calcium channels were increased after P4 treatment. There was an overwhelming decrease in levels of transcripts of genes that are structural constituents of ribosomes with P4 treatment. There was also evidence for gene expression changes in steroid and maturation-related transcripts. Pathway analyses identified cell cycle regulation, insulin action, hedgehog, and B cell activation as pathways containing an over-representation of highly regulated transcripts. Significant regulatory sub-networks of P4-mediated transcripts included genes regulated by tumor protein p53 and E2F transcription factor 1, suggesting that downstream expression targets of these two proteins may be preferentially involved in P4-mediated GVBD. These data provide novel insight into the molecular signaling cascades that underlie P4-signaling in the ovary and identify genes and processes that may indicate premature GVBD due to environmental pollutants that mimic progestins.

The estrous cycle surpasses sex differences in regulating the transcriptome in the rat medial prefrontal cortex and reveals an underlying role of early growth response 1

“…It is important to note, however, that this suggested down-regulation of mitochondrial function and translation in proestrus appears in contradiction with the classically reported enhancing effects of estrogen [ 61 ]. Nevertheless, while estrogen and progesterone both stimulate mitochondrial function when analyzed separately, progestins can antagonize estrogens’ effects in the female rat brain [ 61 ], and extensively down-regulate ribosome-associated genes in other systems [ 59 , 60 ]. This down-regulation in proestrus could thus result from the early rise in progesterone at this stage of the cycle.…”

Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment

“…Global toxicogenomics have been performed with P4 and DRS in zebrafish (Zucchi et al, 2013(Zucchi et al, , 2014 and with P4 in the ovary of fathead minnows (Garcia-Reyero et al, 2013). The advantage of global transcriptomics is its high sensitivity and the potential to discover novel modes of action of a compound.…”

Developmental profiles of progesterone receptor transcripts and molecular responses to gestagen exposure during Silurana tropicalis early development

“…Likewise, P4 exposure also altered transcript levels of srd5αs in fish (D. rerio embryos, Liang et al, 2015b;P. promelas ovary, Chishti et al, 2014;Garcia-Reyero et al, 2013). The major function of srd5α1, 2, and 3 is to convert T to the more potent androgen, 5α-dihydrotestosterone.…”