Exposure to compounds present in
petroleum and
wastewaters from oil and gas extraction sites in the Alberta Oil
Sands Region can impair reproductive health. It has been established that
acid extractable organics found in oil
sands process-affected water (OSPW) such as
naphthenic acids (NA-fraction components; NAFC) can adversely affect reproductive outcomes. We have shown that NAFC exposure results in a significant upregulation of GDF15 in placental trophoblasts, a cellular stress marker known to be involved in human embryonic development and necessary for the maintenance of pregnancy. However, little is known regarding the mechanism(s) underlying NAFC-induced increases in GDF15 production during early placentation. The goal of this study was to examine the effects of NAFC exposure on the regulation of critical
transcription factors of GDF15 in extravillous trophoblast cells. Of these
transcription factors, inflammatory mediators including
prostaglandins have been reported to inhibit proliferation and migration of trophoblast cells in vitro. Hence, the secondary goal of this study was to determine whether
inflammation mediated through
prostaglandin production is critical to GDF15 secretion. HTR-8/SVneo cells were exposed to an NAFC for 6 and 24 h to assess the expression of key transcriptional regulators, GDF15 secretion, and
prostaglandin (
PGE2) output. Treatment with NAFC (125 mg/L only) significantly increased GDF15 expression and secretion in association with upregulation of the
transcription factors KLF4, EGR1, ATF3 and TP53. Similarly,
PTGS2 (i.e. COX2) expression and
PGE2 output were significantly increased at the same concentration. However, co-treatment with a COX2 selective antagonist (
SC236) only partially blocked the NAFC-induced increase in
PGE2 output and did not block GDF15 expression or secretion. These findings suggest that while NAFC may affect GDF15 production, it is not exclusively a result of
prostaglandin-mediated
inflammation. This study provides new insights into the mechanisms by which NAFC may adversely affect placental trophoblast cell function in mammals.