The Toxicologist - Society of Toxicology

1052 MONO-2-ETHYLHEXYL PHTHALATE INCREASES
OXIDANT SPECIES PRODUCTION AND MODIFIES
EXPRESSION OF REDOX-SENSITIVE GENES IN
HUMAN PLACENTAL CELLS.
L. M. Tetz and R. Loch-Caruso. Environmental Health Sciences, University of
Michigan School of Public Health, Ann Arbor, MI.
Di-2-ethylhexyl phthalate (DEHP) is a ubiquitous environmental pollutant used
mainly as a plasticizer in polyvinyl chloride (PVC) products. Mono-ethylhexyl phthalate
(MEHP), the active metabolite of DEHP, increases reactive oxygen species
production and decreases antioxidant levels in liver, kidney, and testicular cells. To
investigate whether the placenta is a potential target of MEHP, we evaluated the effects
of MEHP on production of reactive oxygen species and expression of redoxsensitive
genes in immortalized human placental (extravillous trophoblast) cells
(HTR-8/SVneo). Stimulation of oxidant species generation was assessed by formation
of the fluorescent product 2’,7’-dichlorofluorescein (DCF) in HTR-8/SVneo
cells loaded with 5-(and-6)-carboxy-2’,7’-dichlorodihydrofluorescein diacetate and
exposed for 1 h to dimethyl sulfoxide (DMSO; solvent control), or 12.5, 25, 50,
100 or 200 μM MEHP. MEHP (100 and 200 μM) significantly increased oxidant
species production 90 min after cessation of exposure. RNA expression of 84 redox
sensitive genes was measured in cells exposed to 100 μM MEHP for 4, 8 or 24
hours (n=3 experiments) using a RT-PCR array. Six genes were significantly
changed two-fold or more in cells exposed to MEHP compared to solvent control.
These included oxidative stress-responsive genes (NME5, NOX5, and TXNRD2),
genes important during pregnancy (PTGS2), and genes potentially involved in placental
development (TTN and ANGPTL7). This study shows that MEHP increases
oxidant production and modifies expression of redox-sensitive genes, most
notably, PTGS2, a gene that is necessary for initiation of parturition.
1053 RELATIONSHIP BETWEEN LOW METABOLIC
CAPABILITY OF LIGNANS AND IDIOPATHIC MALE
INFERTILITY.
Y. Xia, P. Zhu, M. Chen, C. Lu, S. Wang and X. Wang. Institute of Toxicology,
Nanjing Medical University, Nanjing, China.
Aim: To investigate the relationships between urinary levels and metabolic capability
of phytoestrogens (PEs) and idiopathic male infertility in Chinese adult males.
Methods: Through eligibility screening procedures, 688 idiopathic infertile men
and 469 fertile controls were recruited. Based on their semen volume, sperm concentration,
sperm number per ejaculum and sperm motility, subjects with idiopathic
infertility were further divided into “normal” and “abnormal” semen quality
groups. By using UPLC-MS/MS, individual exposures to PEs were evaluated by
urinary concentrations of eight PEs or their metabolites (secoisolariciresinol, SEC;
enterolactone, ENL; enterodiol, END; daidzein, DAI; genistein, GEN; equol;
naringin; coumestrol), which were adjusted by creatinine. Results: The median adjusted
isoflavone and lignan concentrations were higher or lower than those in the
U.S reports, respectively. The adjusted SEC, GEN and DAI concentrations of infertile
group were significantly higher than those of control group. Subjects with
higher SEC, GEN and DAI levels were more likely involved in idiopathic male infertility
with abnormal semen quality (P