当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Glutathione deficiency sensitizes cultured embryonic mouse ovaries to benzo[a]pyrene-induced germ cell apoptosis.

Glutathione deficiency sensitizes cultured embryonic mouse ovaries to benzo[a]pyrene-induced germ cell apoptosis.

Abstract：

:Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in glutathione (GSH) synthesis, have decreased tissue GSH. We previously showed that Gclm-/- embryos have increased sensitivity to the prenatal in vivo ovarian toxicity of the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) compared with Gclm+/+ littermates. We also showed that BaP-induced germ cell death in cultured wild type embryonic ovaries is caspase-dependent. Here, we hypothesized that GSH deficiency increases sensitivity of cultured embryonic ovaries to BaP-induced germ cell death. 13.5 days post coitum (dpc) embryonic ovaries of all Gclm genotypes were fixed immediately or cultured for 24 h in media supplemented with DMSO vehicle or 500 ng/ml BaP. The percentage of activated caspase-3 positive germ cells varied significantly among groups. Within each genotype, DMSO and BaP-treated groups had increased germ cell caspase-3 activation compared to uncultured. Gclm+/- ovaries had significantly increased caspase-3 activation with BaP treatment compared to DMSO, and caspase-3 activation increased non-significantly in Gclm-/- ovaries treated with BaP compared to DMSO. There was no statistically significant effect of BaP treatment on germ cell numbers at 24 h, consistent with our prior observations in wild type ovaries, but Gclm-/- ovaries in both cultured groups had lower germ cell numbers than Gclm+/+ ovaries. There were no statistically significant BaP-treatment or genotype-related differences among groups in lipid peroxidation and germ cell proliferation. These data indicate that Gclm heterozygous or homozygous deletion sensitizes embryonic ovaries to BaP- and tissue culture-induced germ cell apoptosis.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Lim J,Luderer U

doi

10.1016/j.taap.2018.05.024

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

38-45

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(18)30235-7

journal_volume

352

pub_type

杂志文章

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