High-fat diet aggravates prenatal low-dose DEHP exposure induced spermatogenesis disorder: Characterization of testicular metabolic patterns in mouse offspring

Fan, Yun; Xu, Qiaoqiao; Qian, Hong; Tao, Chengzhe; Wan, Tingya; Li, Zhi; Yan, Wenkai; Niu, Rui; Huang, Yuna; Chen, Minjian; Xu, Qiujin; Martin, Elizabeth M.; Wang, Xinru; Qin, Yufeng; Lu, Chuncheng

doi:10.1016/j.chemosphere.2022.134296

Cited by 11 publications

(5 citation statements)

References 82 publications

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“…Prenatal exposure of mice to 300 mg/kg DEHP reduced spermatogenesis in male offspring and affected sperm DNA methylation in gene promoters, which are thought to be involved in sperm chemotaxis and posttranscriptional regulatory mechanisms. 23 Similar studies have also found that DEHP damages the reproductive function of male rats, affects the expression of DNA methyltransferase, and leads to a change in the genomic imprinted methylation pattern that is passed on to the next generation, which unbalances the key role of imprinted genes in the male reproductive system and eventually leads to cryptorchidism in offspring. 24 Although our study is the first to characterize the transcriptome and proteome of a DEHP-induced mouse model of DNA damage, it has been found that DEHP may affect semen quality by causing dysregulation of seminal plasma polyunsaturated fatty acids (PUFAs) and acylcarnitine metabolism.…”

Section: Discussionmentioning

confidence: 82%

“…A high-fat diet can increase the degree of testicular riboflavin and biotin metabolism induced by DEHP. 23 Another category enriched in our results is pathways in cancer. The risk of cancer from exposure to DEHP in ambient air is below the acceptable limit (10 À6 ), but in indoor and occupational settings, the risk of cancer is serious even for short periods of exposure (2 years).…”

Section: Discussionmentioning

confidence: 84%

“…A high-fat diet can increase the degree of testicular riboflavin and biotin metabolism induced by DEHP. 23…”

Section: Discussionmentioning

confidence: 99%

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Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model

et al. 2022

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Di(2-ethylhexyl) phthalate (DEHP) is one of the most common organic pollutants and is added to various plastic products as a plasticizer. DEHP oxidative metabolite content in the human body is associated with DNA damage in sperm and decreased testosterone levels in blood. In this study, a DEHP-induced sperm DNA damage mouse model was replicated and improved, and the transcriptomic and proteomic characteristics of the model were observed. Male mice in the two groups were exposed to DEHP 1 g/kg/d or the same amount of normal saline for 60 days, and the sperm DNA fragmentation index (DFI) was detected by a sperm chromatin structure assay (SCSA). The mRNA and protein expression profiles of the testis were detected by RNA-seq and data-independent acquisition (DIA). The sperm DFI of the DEHP group was significantly increased. Compared with the control group, 111 differentially expressed genes (DEGs) and 2147 differentially expressed proteins (DEPs), such as Lamb2, Ahnak, Tkt, Dnah8 and Tbl2, were found in the DEHP group. These genes were mainly enriched in metabolic pathways, pathways in cancer and the PI3K-Akt signaling pathway. Our results showed that DEHP 1 g/kg/d can induce sperm DNA damage in a male mouse model after 60 days of intragastric administration. The reproductive toxicity of DEHP may be related to metabolic pathways in cancer and the PI3K-Akt signaling pathway.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 84%

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Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model

et al. 2022

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“…DEHP has been proved to cause apoptosis in mouse sperm . Previous experiments have shown that exposure to DEHP during fetal gland development activated the PI3K/AKT pathway of mice to produce reproductive toxicity .…”

Section: Discussionmentioning

confidence: 99%

“…DEHP has been proved to cause apoptosis in mouse sperm. 48 Previous experiments have shown that exposure to DEHP during fetal gland development activated the PI3K/ AKT pathway of mice to produce reproductive toxicity. 49 By successfully building the DEHP-PI3K docking model, we suggested that DEHP activated the PI3K/AKT pathway in the mouse cerebrum.…”

Section: Dehp and Mps Evoke Oxidative Stress And Induce Antioxidant C...mentioning

confidence: 99%

Di-(2-Ethylhexyl) Phthalate and Microplastics Induced Neuronal Apoptosis through the PI3K/AKT Pathway and Mitochondrial Dysfunction

Zhang

Sun

et al. 2022

J. Agric. Food Chem.

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Di-(2-Ethylhexyl) phthalate (DEHP) and microplastics (MPs) have released widespread residues to the environment and possess the ability to cause damage to humans and animals. However, there are still gaps in the study of damage to neurons caused by DEHP and MPs in mice cerebra and whether they have combined toxic effects. To investigate the underlying mechanism of action, mice were fed 200 mg/kg DEHP and 10 mg/L MPs in vivo. In vitro, NS20Y (CBNumber: CB15474825) cells were treated with 25 μM DEHP and 775 mg/L MPs. Next, qRT-PCR and western blot analysis were performed to evaluate PI3K/AKT pathway genes, mitochondrial dynamics-related genes, apoptosis-related genes, and GSK-3β and its associated genes, mRNA, and protein expression. To determine pathological changes in the mice cerebra, hematoxylin and eosin (H&E) staining, transmission electron microscopy, and TUNEL staining were employed. To determine the levels of reactive oxygen species (ROS) and apoptosis cells in vitro, ROS staining, acridine orange/ethidium bromide (AO/EB) staining, and flow cytometry were performed. Our results demonstrated that DEHP and MPs caused changes in mitochondrial function, and GSK-3β and its associated gene expression in mice through the PI3K/AKT pathway, which eventually led to apoptosis of neurons. Moreover, our findings showed that DEHP and MPs have a combined toxic effect on mice cerebra. Our findings facilitate the understanding of the neurotoxic effects of DEHP and MPs on neurons in the cerebra of mice and help identify the important role of maintaining normal mitochondrial function in protecting cerebrum health.

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Wuzi Yanzong Pill alleviates spermatogenesis dysfunction by modulating the gut microbial tryptophan metabolites

Liu,

Feng,

Zhang

et al. 2024

Arabian Journal of Chemistry

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High-fat diet aggravates prenatal low-dose DEHP exposure induced spermatogenesis disorder: Characterization of testicular metabolic patterns in mouse offspring

Cited by 11 publications

References 82 publications

Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model

Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model

Di-(2-Ethylhexyl) Phthalate and Microplastics Induced Neuronal Apoptosis through the PI3K/AKT Pathway and Mitochondrial Dysfunction

Wuzi Yanzong Pill alleviates spermatogenesis dysfunction by modulating the gut microbial tryptophan metabolites

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