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

Overview

Journal Toxicol Sci

Publisher Oxford University Press

Specialty Toxicology

Date 2012 Jan 19

PMID 22253057

Citations 12

Authors

Brooke N Nakamura

Isaac Mohar

Gregory W Lawson

Mabel M Cortes

Yvonne D Hoang

Laura Ortiz

Reshma Patel

Bogdan A Rau

Lisa A McConnachie

Terrance J Kavanagh

Ulrike Luderer

Affiliations

Soon will be listed here.

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.

Citing Articles

Human sperm proteome reveals the effect of environmental borne seminal polyaromatic hydrocarbons exposome in etiology of idiopathic male factor infertility.

Nayak J, Jena S, Kumar S, Kar S, Dixit A, Samanta L Front Cell Dev Biol. 2023; 11:1117155.

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Prenatal exposure to benzo[a]pyrene depletes ovarian reserve and masculinizes embryonic ovarian germ cell transcriptome transgenerationally.

Lim J, Shioda T, Malott K, Shioda K, Odajima J, Leon Parada K Sci Rep. 2023; 13(1):8671.

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Sex Differences in Embryonic Gonad Transcriptomes and Benzo[a]pyrene Metabolite Levels After Transplacental Exposure.

Lim J, Ramesh A, Shioda T, Leon Parada K, Luderer U Endocrinology. 2021; 163(1).

PMID: 34734245 PMC: 8633617. DOI: 10.1210/endocr/bqab228.

In Utero Exposure to Benzo[a]pyrene Induces Ovarian Mutations at Doses That Deplete Ovarian Follicles in Mice.

Luderer U, Meier M, Lawson G, Beal M, Yauk C, Marchetti F Environ Mol Mutagen. 2018; 60(5):410-420.

PMID: 30353947 PMC: 6615722. DOI: 10.1002/em.22261.

Environmental PAH exposure and male idiopathic infertility: a review on early life exposures and adult diagnosis.

Madeen E, Williams D Rev Environ Health. 2016; 32(1-2):73-81.

PMID: 27935856 PMC: 5454023. DOI: 10.1515/reveh-2016-0045.

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