Glutathione deficiency sensitizes cultured embryonic mouse ovaries to benzo[a]pyrene-induced germ cell apoptosis
Autor: | Ulrike Luderer, Jinhwan Lim |
---|---|
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Embryonic Germ Cells animal structures Embryonic ovary Knockout Glutamate-Cysteine Ligase Ovary Apoptosis Gestational Age Inbred C57BL Toxicology Article Andrology Tissue Culture Techniques 03 medical and health sciences chemistry.chemical_compound Mice Germ cell proliferation medicine Germ cells Genetics polycyclic compounds Benzo(a)pyrene Animals Pharmacology Mice Knockout Chemistry GCLM organic chemicals Embryo Glutathione Pharmacology and Pharmaceutical Sciences Glutamate cysteine ligase modifier subunit Mice Inbred C57BL Benzo[a]pyrene 030104 developmental biology medicine.anatomical_structure Cytoprotection embryonic structures Female Germ cell |
Zdroj: | Toxicology and applied pharmacology. 352 |
ISSN: | 1096-0333 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |