Integrated transcriptome and metabolomic analyses uncover the mechanism of cadmium-caused mouse spermatogonia apoptosis via inducing endoplasmic reticulum stress
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引用次数: 0
Abstract
Cadmium (Cd) is a well-recognized male reproductive toxicant that can cause testicular germ cell apoptosis. However, the underlying mechanism needs investigation. CG-1 mouse spermatogonia (spg) cells were treated with 20 μM cadmium chloride (CdCl2) for 24 h. Cell apoptosis was measured, and the expressions of key genes and protein biomarkers involved in endoplasmic reticulum (ER) stress were detected, respectively. Untargeted metabolomics was performed to identify different metabolites, and transcriptome analysis was conducted to screen differentially expressed genes (DEGs). Our results indicated that CdCl2 exposure caused cell apoptosis, and DEGs were involved in several apoptosis-related pathways. Moreover, CdCl2 exposure apparently increased the mRNA and protein expressions levels of both GRP78 and ATF6α, disrupting the expression of various metabolites, particularly amino acids. Conclusively, our study reveals the pathway of CdCl2 toxicity on mouse spg, providing a deep understanding of CdCl2-induced testicular toxicity.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.