Transcriptional
and Physiological Responses Induced
by Binary Mixtures of Drospirenone and Progesterone in Zebrafish (<i>Danio rerio</i>)
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Abstract
Drospirenone (DRS) is a synthetic
progestin increasingly used in
oral contraceptives with similar effects to progesterone (P4). Wild
fish are exposed to DRS and P4 through wastewater. However, the effects
of DRS on fish, both as an individual compound and in mixtures, have
not been extensively studied. Therefore, in this study, global gene
expression profiles of ovary and brain of female zebrafish (<i>Danio rerio</i>) were characterized after exposure to 55, 553,
and 5442 ng/L DRS for 14 days. The effects were then compared to the
observed responses after exposure to mixtures of DRS and P4 (DRS+P4:
27 + 0.8, 277 + 8 and 3118 + 123 ng/L). Transcriptomics findings were
related to the changes in vitellogenin protein concentrations in the
blood, morphology, and histology of gonads. Multivariate analysis
indicated tissue-, dose-, and treatment-dependent expression profiles.
Genes involved in steroid hormone receptor activity and circadian
rhythm were enriched in DRS and mixture groups, among other pathways.
In mixtures, the magnitude of response was dose- and transcript-dependent,
both at the molecular and physiological levels. Effects of DRS and
P4 were additive for most of the investigated parameters and occurred
at environmentally relevant concentrations. They may translate to
adverse reproductive effects in fish