NDLI: Increased Sensitivity to Testicular Toxicity of Transplacental Benzo[a]pyrene Exposure in Male Glutamate Cysteine Ligase Modifier Subunit Knockout (Gclm−/−) Mice

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Increased Sensitivity to Testicular Toxicity of Transplacental Benzo[a]pyrene Exposure in Male Glutamate Cysteine Ligase Modifier Subunit Knockout (Gclm−/−) Mice

Early Growth Response Factor-1 Limits Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice

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Increased Sensitivity to Testicular Toxicity of Transplacental Benzo[a]pyrene Exposure in Male Glutamate Cysteine Ligase Modifier Subunit Knockout (Gclm−/−) Mice

Content Provider	PubMed Central
Author	Nakamura, Brooke N. Mohar, Isaac Lawson, Gregory W. Cortés, Mabel M. Hoang, Yvonne D. Ortiz, Laura Patel, Reshma Rau, Bogdan A. Mcconnachie, Lisa A. Kavanagh, Terrance J. Luderer, Ulrike
Copyright Year	2012
Abstract	Polycyclic aromatic hydrocarbons (PAHs), like benzo[a]pyrene (BaP), are ubiquitous environmental pollutants formed by the incomplete combustion of organic materials. The tripeptide glutathione (GSH) is a major antioxidant and is important in detoxification of PAH metabolites. Mice null for the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH concentrations. We investigated the effects of Gclm deletion alone on male fertility and spermatogenesis and its effect on the sensitivity of male embryos to the transplacental testicular toxicity of BaP. Gclm−/− males had dramatically decreased testicular and epididymal GCL enzymatic activity and total GSH concentrations compared with Gclm+/+ littermates. Ratios of reduced to oxidized GSH were significantly increased in Gclm−/− testes. GSH reductase enzymatic activity was increased in Gclm−/− epididymides. We observed no changes in fertility, testicular weights, testicular sperm head counts, or testicular histology and subtle changes in cauda epididymal sperm counts, motility, and morphology in Gclm−/− compared with Gclm+/+ males. Prenatal exposure to BaP from gestational day 7 to 16 was dose dependently associated with significantly decreased testicular and epididymal weights, testicular and epididymal sperm counts, and with vacuolated seminiferous tubules at 10 weeks of age. Gclm−/− males exposed prenatally to BaP had greater decreases in testicular weights, testicular sperm head counts, epididymal sperm counts, and epididymal sperm motility than Gclm+/+ littermates. These results show no effects of Gclm deletion alone on male fertility and testicular spermatogenesis and subtle epididymal effects but support increased sensitivity of Gclm−/− males to the transplacental testicular toxicity of BaP.
Related Links	http://dx.doi.org/10.1093/toxsci/kfs017
Starting Page	227
File Format	PDF
ISSN	10960929
e-ISSN	10960929
Journal	Toxicological Sciences
Issue Number	1
Volume Number	126
Language	English
Publisher	Oxford University Press
Publisher Date	2012-03-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Toxicology

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Increased Sensitivity to Testicular Toxicity of Transplacental Benzo[a]pyrene Exposure in Male Glutamate Cysteine Ligase Modifier Subunit Knockout (Gclm−/−) Mice

Drosophila melanogaster Glutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form

Lack of Maternal Glutamate Cysteine Ligase Modifier Subunit (Gclm) Decreases Oocyte Glutathione Concentrations and Disrupts Preimplantation Development in Mice

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Levels of Kras Codon 12 Mutations in Mouse Ovary Measured by ACB-PCR Were Not Increased by Transplacental Exposure to benzo[a]pyrene or Impacted by Gclm Genotype

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Influence of Exposure to Benzo[a]pyrene on Mice Testicular Germ Cells during Spermatogenesis

Increased Sensitivity to Testicular Toxicity of Transplacental Benzo[a]pyrene Exposure in Male Glutamate Cysteine Ligase Modifier Subunit Knockout (Gclm−/−) Mice

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