|dc.description.abstract||The ability of POPs (persistent organic pollutants) to act as endocrine disruptors and their
potential role in negative trends in male reproductive health have caused increased concern
over the last few decades. There has been an increased focus on the endocrine disrupting
capacity of environmental mixtures of pollutants, compared to earlier focus on single
compound exposure studies.
While Norwegian health authorities strongly recommend a higher consumption of fish and
fish liver oil dietary supplements because of their beneficial health effects, they have been put
forward as considerable sources of human intake of POPs.
Leydig cells are responsible for the biosynthesis of testosterone, which is essential for male
developmental and reproductive function. The predominant steroid biosynthesis Δ5 pathway is
similar in pig and human. Thus, the porcine Leydig cell provides a useful model for
investigating human testicular steroidogenesis.
The aim of this study was to investigate the effects of POPs in three marine mixtures (“Cod”,
“Waste” and “Tran”), representing different steps in the refinement process of cod liver oil
used as a dietary supplement, on steroidogenesis in LH-stimulated primary porcine Leydig
cells. The investigation of effects was performed through a holistic approach, including
exploration of hormone production and regulation of genes involved in steroidogenesis,
epigenetic and anti-oxidative mechanisms. In addition to the aspect of achieving a better
understanding of the effect of POPs in mixtures on steroidogenesis, we also compared effects
of the three mixtures. The mixtures gave three different exposure scenarios; exposure to
“Cod” mixture (POPs extracted from crude cod liver oil), “Waste” mixture (POPs extracted
from waste from the refinement process, containing mainly non-dioxin-like POPs) and “Tran”
mixture (POPs extracted from finished cod liver oil dietary supplement).
Environmentally relevant doses of the marine mixtures of POPs had a disrupting effect on
steroidogenesis in primary LH-stimulated porcine Leydig cells. The “Cod”, “Waste” and
“Tran” mixtures had a generally inhibitory effect on testosterone and 17β-estradiol
production. The expression pattern of genes involved in steroidogenesis was decreased
expression after exposure to all three mixtures. The decrease in gene expression could explain
the altered hormone production in exposed cells. There was a trend towards decreased
expression aof genes involved in epigenetics and anti-oxidative mechanisms after exposure to
the “Tran” mixture.
The fact that endocrine disrupting effects were observed also with the “Tran” mixture,
representing pollutants extracted from purified cod liver oil for human consumption, gives
reason for concern. The beneficial effects of fish consumption and intake of cod liver oil
supplements should be balanced against the increased exposure to POPs and their potential
ability to exert negative health effects. Further investigation should be carried out to elucidate
wether the endocrine disruption after “Tran” mixture exposure also occurs in vivo.||en_US